In the news

F1000 Article Recommendation

Hydrogen sulphide (H2S) is a key signalling molecule in higher eukaryotes and is regarded as the third ‘gasotransmitter’ or small signalling molecule (after NO and CO). It regulates physiological processes in higher animals and is an antimicrobial agent. It is also generated endogenously in animals and microbes and in the latter has been shown to protect cells against antibiotics. Here Mironov and colleagues identify 3-mercaptopyruvate sulfurtransferase as the major source of H2S in E. coli; resistance to exogenous H2O2 is dependent on this enzyme. A model is proposed linking cysteine metabolism, H2S and oxidative stress.

sRNA-Mediated Control of Transcription Termination in E. coli.

This study reports a novel role for bacterial small RNAs (sRNAs): preventing Rho-dependent transcription termination. Sedlyarova et al. demonstrate that many Escherichia coli genes contain long (>80nt) 5’UTRs that are sites of Rho termination.

Fighting Antibiotic Resistance Through Deeper Sequencing

Researchers developed a new technique to uncover rare mutations in the bacterial genome and used it to determine how certain antibiotics mutate DNA. How will this approach help combat antibiotic resistance? Find out...

Maximum-Depth Sequencing Detects Extremely Rare Variants, Has Potential Clinical Applications

NEW YORK (GenomeWeb) – Researchers from New York University have developed a method for detecting very rare mutations in a population of cells using error-corrected sequencing. The approach, called maximum-depth sequencing (MDS), adds barcode and adaptor sequences directly onto a short sequence of interest so it can be amplified and sequenced many times in parallel to produce a consensus sequence. In so doing, explained co-senior author Evgeny Nudler, a professor of biochemistry and molecular pharmacology at New York University School of Medicine, the approach applies "all the power of a high-throughput sequencing machine on a small region."

Exogenous Hsp70 delays senescence and improves cognitive function in aging mice.

The impressive takeaway messages of this publication are given in its title, that recombinant human Hsp70 (presumably the stress-induced form) can be administered intranasally as a therapeutic agent to maintain cognitive function and to extend lifespan in aging mice.

Sequencing method precise enough to reveal mechanisms by which bacteria resist antibiotics

A new technology can read the order (sequence) of the "letters" making up DNA code with enough accuracy to reveal how bacteria use high-speed evolution to defeat antibiotics. That is the finding of a study led by researchers at NYU Langone Medical Center and published June 22 in the journal Nature. The technology, called Maximum Depth Sequencing (MDS), eliminates the error introduced by core methods behind current high-speed DNA sequencing machines to catch genetic changes so rare that older methods could not tell them apart from machine error.

Sequencing method precise enough to reveal mechanisms by which bacteria resist antibiotics

A new technology can read the order (sequence) of the "letters" making up DNA code with enough accuracy to reveal how bacteria use high-speed evolution to defeat antibiotics. That is the finding of a study led by researchers at NYU Langone Medical Center and published June 22 in the journal Nature.

Bacteria Survive Antibiotic Assault Due To DNA Repair Mechanisms

Researchers at NYU Langone Medical Center have identified a key molecule which allows bacteria to repair serious DNA damage, thereby making them resistant to certain antibiotics. The research was published in the journal, Science. According to the study authors, designing future antibiotic treatments to target this molecule – called ppGpp – could make these microbes more susceptible to irreparable DNA damage, and cell death. Antibiotic resistance is developed when bacteria are repeatedly exposed to the same drug. According to the Centers for Disease Control and Prevention (CDC), drug-resistant bacterial infections are linked to 2 million cases of illness, and 23,000 deaths in the US each year.

Factor Preserves DNA Integrity in Bacteria Despite Assault from Antibiotics

NEW YORK, May 19, 2016 /PRNewswire-USNewswire/ -- A key biochemical enables bacteria to repair otherwise fatal damage to their DNA, including that caused by antibiotics. That is the finding of a study led by researchers at NYU Langone Medical Center and published May 20 in the journal Science.

Chronic Exogenous Hsp70 Administration Has Cognitive, Behavioral, and Molecular Neuroprotective Effects on Aging Mice

Heat Shock Protein 70 (Hsp70) is a molecular chaperone that plays a protective role in various neurodegenerative disorders associated with aging, but its synthesis, induction, and activity in neuronal tissues decrease with age. As intranasally injected Hsp70 can enter murine neurons, Evgeny Nudler and his team explored the effect of exogenous Hsp70 on longevity

Scientists Identify the Master Regulator of Cells’ Heat Shock Response, Pointing to New Potential Targets for Neurodegenerative Diseases and Cancer

Heat shock proteins protect the molecules in all human and animal cells with factors that regulate their production and work as thermostats. In new research published Sept. 16 in the journal eLife, scientists at NYU Langone Medical Center and elsewhere report for the first time that a protein called translation elongation factor eEF1A1 orchestrates the entire process of the heat shock response. By doing so, eEF1A1 supports overall protein homeostasis inside the cell, ensuring that it functions properly under various internal and external stress conditions. The researchers suggest that this finding could reveal a promising, new drug target for neurodegenerative diseases and cancer.

DNA Damage Scout

Long known for its role in transcribing the genome’s code into messenger RNAs that can be translated into proteins, the enzyme RNA polymerase may also survey the genome for damage. That’s according to a study led by investigators at the New York University Langone Medical Center, which was published last month (January 8) in Nature. Biochemist Evgeny Nudler and his colleagues have described one way in which bacterial cells rely on RNA polymerase to start repairing DNA damage, which, the authors added, hint at pervasive transcription—the surprising revelation of noncoding RNA molecules and an axis of debate in molecular biology.

UvrD facilitates DNA repair by pulling RNA polymerase backwards

Nucleotide excision repair is a DNA damage repair pathway that removes a variety of DNA lesions, including UV-induced thymine dimers. UvrD is a DNA-dependent DNA helicase required for nucleotide excision repair in E. coli. In this work, Epshtein et al. demonstrate that UvrD is an RNA polymerase-binding protein. The authors also show that UvrD promotes backwards sliding, or 'backtracking', of RNA polymerase at numerous positions along the DNA, an activity dependent on its ATP-binding motif.

Molecular biology: The tug of DNA repair

The transcription enzyme RNA polymerase stalls at DNA lesions, hindering their repair. Accessory factors dislodge the enzyme by pushing it forwards, but a study finds that pulling it backwards may also be effective.

Enzyme Reverses Stalled Transcription Machinery to Aid DNA Repair

Rather like a train halted by damaged rails is hauled away, the better to expose the rails to repair crews, RNA polymerase that is snagged by a faulty stretch of DNA can be pulled backwards by an enzyme, a transcription elongation factor with helicase/translocase activity. This enzyme appears to play an essential role in nucleotide excision repair, helping RNA polymerase backtrack when necessary, facilitating its transcriptional role, and even enabling it to serve a damage-scanning function.

Molecular engines star in new model of DNA repair

Our health depends in large part upon the ability of specialized enzymes to find and repair the constant barrage of DNA damage brought on by ultraviolet light radiation and other sources. In a new study NYU School of Medicine researchers reveal how an enzyme called RNA polymerase patrols the genome for DNA damage and helps recruit partners to repair it. The result: fewer mutations and consequently less cancer and other kinds of disease.

NYU Langone Medical Center researcher named Howard Hughes Investigator

NEW YORK, May 9, 2013 – The Howard Hughes Medical Institute (HHMI) has announced the appointment of Evgeny Nudler, PhD, to the 2013 class of HHMI Investigators.The appointment ranks as one of the highest honors that can be bestowed on a biomedical research scientist. Dr. Nudler, the Julie Wilson Anderson Professor of Biochemistry in the Department of Biochemistry and Molecular Pharmacology at NYU Langone Medical Center, was selected among more than 1,200 applicants for his work on numerous biochemical frontiers, including the role of bacterial gases in antibiotic resistance and the interplay between RNA transcription and the cellular response to stress.

The 2013 HHMI Investigators

Taking risks and venturing into new areas of research have been common threads in Evgeny Nudler’s career. He has made major discoveries in topics as diverse as the mechanics of RNA synthesis, cellular adaptations to stress, and bacterial resistance to antibiotics.

F1000 evaluation

This article describes a very interesting example of interspecies signaling between commensal bacteria and their Caenorhabditis elegans worm host. This worm does not contain a gene encoding nitric oxide synthase (NOS) and, thus, does not produce NO via this enzyme. Bacteria that feed the worm provide the bacterial enzyme, resulting in the generation of NO. The worms show enhanced longevity and stress resistance as a result of NO-enhanced signaling via the HSF-1 and DAF-16 transcription factors.

Study shows nitric oxide may increase life span Read more: http://www.digitaljournal.com/article/343375#ixzz2L4myjPHv

Research has shown that nitric oxide increases circulation and can be beneficial to those suffering from hypertension and congestive heart failure, but a new study suggests it may also increase our overall life span.

Nitric Oxide: A Little Molecule's Remarkable Feat -- Prolonging Life, Worm Study Shows

Nitric oxide, the versatile gas that helps increase blood flow, transmit nerve signals, and regulate immune function, appears to perform one more biological feat -- prolonging the life of an organism and fortifying it against environmental stress, according to a new study.

Gut Bacteria Influence Worms’ Lifespans

It’s not as exciting as El Dorado’s source of eternal youth, but nitric oxide-producing bacteria are extending the lifespan of the humble roundworm Caenorhabditis elegans. The worm lacks the enzyme needed to produce nitric oxide. In animals which are capable of manufacturing nitric oxide, it has been shown to increase blood flow, promote efficient nerve signal transmission and regulate the immune system, all factors that may contribute to a longer lifespan.

Bacterial transcription: Rho gets to grips with the riboswitch

Riboswitches have emerged as an important class of regulatory elements that control the fate of bacterial mRNAs. These RNA structures are located upstream of the coding region of many mRNAs and, in response to the binding of specific metabolites or ions, the mRNA structure is altered, typically blocking expression of the encoded protein. Two general mechanisms of riboswitch action have previously been described; the first relies on the formation of an intrinsic transcription terminator, and the second on sequestration of the ribosome-binding site or start codon. Hollands et al. now show that a third general mechanism exists in both Salmonella enterica subsp. enterica serovar Typhimurium and Escherichia coli that uses the RNA helicase, Rho, to attenuate transcription.

F1000 Evaluation

This thorough research surprisingly establishes a cytoprotectant role for hydrogen sulfide (H2S) production by non-sulfur bacteria growing aerobically. While this gas has been shown in mammals to have signaling properties that are similar to nitric oxide (NO), no apparent role for low levels of H2S had been demonstrated in bacteria. It had long been known that many bacteria produce low levels of H2S that were thought to be a byproduct of sulfur amino acid metabolism. Of special interest was the demonstration here that diverse species of pathogens were more resistant to antibiotics when producing H2S.

F1000 Evaluation

This paper describes a structural model of the antibiotic tagetitoxin (Tgt) bound to the transcription elongation complex (TEC) of bacterial RNA polymerase, which was prepared by molecular dynamic simulation. This model proposed a new Tgt binding site, which is not the same one as found in the X-ray crystal structure of RNA polymerase {1}, and Tgt complex, and provides new insight into how Tgt inhibits RNA polymerase activity.

Antimicrobials: Promoting tolerance

Tolerance to antibiotics in genetically susceptible bacteria poses major problems for the treatment of infectious diseases and provides a source of resistant strains. Two papers published in Science now provide insight into the diverse mechanisms underlying this process.

New Clues for Improving Antibiotics for Tolerant Bacteria

Some of the ways bacteria protect themselves from antibiotics might be used against them to strengthen existing drugs

Antioxidant Strategies to Tolerate Antibiotics

In living organisms, aerobic metabolism produces toxic reactive oxygen species (ROS) (1). Life can thus be seen as a balance between metabolic rate and a cell's ability to detoxify ROS. This understanding has led to intense public interest and increased consumption of dietary antioxidants. Although the effectiveness of antioxidant supplements is not yet established, there is no doubt that eukaryotic and prokaryotic cells have developed efficient endogenous antioxidant mechanisms (1, 2). On pages 982 and 986 of this issue, Nguyen et al. (3) and Shatalin et al. (4) describe two such mechanisms that confer antibiotic tolerance in bacteria.

Targeting Bacterial Gas Defenses Allow for Increased Efficacy of Numerous Antibiotics

Although scientists have known for centuries that many bacteria produce hydrogen sulfide (H2S) it was thought to be simply a toxic by-product of cellular activity. Now, researchers at NYU School of Medicine have discovered H2S in fact plays a major role in protecting bacteria from the effects of numerous different antibiotics.

Linking RNA polymerase backtracking to genome instability in E. coli.

In this report, Dutta and colleagues provide an explanation for how active translation maintains the integrity of the Escherichia coli genome. The authors find that clashes between the transcription and replication machinery cause double-strand breaks in E. coli due to RNA polymerase backtracking on the gene. These breaks are prevented by the Mfd helicase (a super family II helicase that removes stalled transcription elongation factors) during co-directional collisions but not during head-on collision between the transcription machinery and the replisome.

NYU Langone Researchers Reveal A New Mechanism Of Genomic Instability

Researchers at NYU School of Medicine have discovered the cellular mechanisms that normally generate chromosomal breaks in bacteria such as E. coli. The study’s findings are published in Cell. “This study provides a new explanation on how bacteria generate mutations and adapt to stressors like antibiotics. The study is quite unusual as it touches on several different fields of molecular biology at the same time: replication, transcription, translation and DNA repair,” said Evgeny Nudler, PhD, The Julie Wilson Anderson Professor of Biochemistry, in the Department of Biochemistry at NYU School of Medicine and co-author of the study.

NYU Langone Medical Center's Evgeny Nudler Receives 2010 Blavatnik Award for Young Scientists for His Breakthrough Research

NYU Langone Medical Center announced that Evgeny Nudler, PhD, the Julie Wilson Anderson Professor of Biochemistry at NYU School of Medicine, was awarded the prestigious 2010 Blavatnik Award for Young Scientists for his highly innovative, impactful, and interdisciplinary accomplishments in science. In addition to being recognized for his extraordinary successes in research, he will receive $25,000 in unrestricted funds which is provided to support promising scientists early in their careers.

Blavatnik Awards 2010 Winners

Congratulations to the winners and finalists of the fourth annual Blavatnik Awards for Young Scientists! Of the 12 scientists from the tri-state area selected as finalists for their outstanding work as postdoctoral fellows and faculty members, 7 winners were selected:

Cooperation between translating ribosomes and RNA polymerase in transcription elongation.

This elegant study demonstrates direct cooperation between ribosomes and RNA polymerase resulting in translation-transcription coupling in bacteria. The presented results suggest that translating ribosomes stimulate transcription by preventing backtracking of RNA polymerase.

Syntheses That Stay Together

An old principle of macromolecular biosynthesis in bacteria is that the speed of protein synthesis (translation) matches that of messenger RNA (mRNA) synthesis (transcription), but how this integration occurs has not been clearly defined. An obvious conjecture is that ribosomes move along the emerging mRNA at whatever speed RNA polymerase goes so that translation and transcription remain coordinated, as it is known to do when conditions change (1). However, on page 504 (2) and 501 (3) of this issue, Proshkin et al. and Burmann et al., respectively, suggest the opposite: Efficient binding and progression of ribosomes along mRNA increase the speed of RNA polymerase, whereas the absence of ribosomes allows the polymerase to slow and wait for ribosomes to catch up.

Rho and RNAP Finally Tie the Knot

Could allostery also be critical for Rho-dependent transcription termination in bacteria? The RNA helicase Rho uses the energy of ATP hydrolysis to move along an emerging nascent strand of RNA. When Rho reaches an actively transcribing RNA polymerase (RNAP), it disrupts elongation, and the RNAP molecule falls off the template DNA. Recent X-ray structures of Rho in a complex with RNA provide stunning details of Rho's translocation mechanism, but how Rho forces RNAP to dissociate from DNA and RNA is still unknown. Now, Epshtein et al. (2010) present compelling evidence that RNAP plays an active role in Rho-dependent termination.

Paradigm Changing Mechanism Is Revealed for the Control of Gene Expression in Bacteria

A new study led by researchers at NYU Langone Medical Center is shedding new light on the action of Rho, a key regulatory protein in E. coli and many other bacteria. The study published in the January 14, 2010 issue of Nature reveals a new paradigm to understand the molecular principles of gene transcription. This work could potentially lead to the development of new types of antibiotics that could target Rho and its crucial functions.

When It Comes to Antibiotics, Bacteria Show Some NO-how

Homologs to mammalian nitric oxide synthases are found in many mostly Gram-positive bacteria. In some genera such as bacilli, and staphylococci, the NO these enzymes produce protects against oxidative damage, this effect has now been shown to provide an advantage against antibiotics that kill by increasing cellular levels of reactive oxygen species.

Nitric Oxide Holds Promise for Better Antibiotics

Tough pathogens, such as anthrax and MRSA, depend on nitric oxide to defend themselves against antibiotic drugs, according to recent research. Targeting this line of defense may lead to new tactics for fighting even the nastiest bacterial infections. Although doctors have prescribed antibiotics to treat infections for well over 50 years, many bacteria have developed resistance to these treatments, prompting drug companies to spend millions of dollars developing alternative forms of the drugs. Even more troublesome have been specific bacteria, including strains of Staphylococcus, which defy most known antibiotics. Yet, with the new discovery of how bacteria defend themselves with nitric oxide, scientists now hope that by merely blocking the site of nitric oxide production in bacteria they can make traditional antibiotics much more potent against even incredibly virulent infections.

F1000 Evaluation

In this landmark study Gusarov et al. demonstrate that loss of the nitric oxide synthase (NOS) gene in Bacillus subtilis renders the bacteria hypersusceptible to a diverse panel of antimicrobials, including classical antibiotics. Bacterial NOS, therefore, represents a novel target for antibiotic development, which is an important issue in this age of multidrug resistant bacteria.

Bacteria Say NO To Drugs

Many species of bacteria express enzymes that synthesize nitric oxide (NO) from arginine, but so far the physiological role of such bacterial NO synthases has been a mystery. Now, Evgeny Nudler and colleagues at New York University School of Medicine have shown that endogenously produced NO protects bacteria from a broad spectrum of natural and synthetic antibiotics (Science 2009, 325, 1380). Their results suggest that inhibiting NO synthase in disease-causing bacteria could enhance the efficacy of antimicrobial therapy.

Antibiotic resistance clue found

US scientists have uncovered a defence mechanism in bacteria that allows them to fend off the threat of antibiotics. It is hoped the findings could help researchers boost the effectiveness of existing treatments. The study published in Science found that nitric oxide produced by the bacteria eliminates some key effects of a wide range of antibiotics.

Scientists Find Way To Make Bacteria More Vulnerable To Existing Antibiotics

A team of scientists in the US reports they may have a found a new way to make bacteria like MRSA and anthrax more vulnerable to existing antibiotics by interfering with a defence mechanism that the microbes use to resist the oxidative stress imposed on them by antibiotics.

NO Good: Nitric Oxide May Be Key to Overcoming Antibiotic Resistance

Researchers may be a touch closer to eliminating antibiotic-resistant bacteria, such as MRSA (methicillin-resistant Staphylococcus aureus) and anthrax, thanks to a troublesome air pollutant—nitric oxide (NO).

Study exposes how bacteria resist antibiotics

Scientists have discovered how bacteria fend off a wide range of antibiotics, and blocking that defense mechanism could give existing antibiotics more power to fight dangerous infections.

F1000 Evaluation

This paper shows the remarkable involvement of Rho factor on the control of transcription of "newly acquired" or foreign DNA in Escherichia coli strains. In the absence of Rho function, achieved by inhibition with bicyclomycin (BCM), whole genome arrays revealed the upregulation of strain-specific genes presumably acquired through horizontal gene transfer or phage infection.

Microbiology Select

Bacteria are one of the most diverse groups of organisms on our planet and are exquisitely adapted for survival in diverse environments ranging from the human digestive tract to deep-sea hydrothermal vents. As bacteria have evolved to optimally inhabit and exploit their host environments, so too have their hosts changed in response to the presence of these prokaryote interlopers. This issue's Microbiology Select highlights recent findings that shed light on the interactions of bacteria with their environments as well as the beneficial contributions that some bacteria make to their hosts.

Genetics: Self defence

An 'immune system' embedded in Escherichia coli's genome protects the bacterium against injurious genes acquired from other organisms. A protein called Rho helps E. coli produce some RNA molecules because it indicates when to stop making them. Evgeny Nudler of New York University School of Medicine, Max Gottesman of Columbia University Medical Center, New York, and their team exposed E. coli to an antibiotic called bicyclomycin that inhibits Rho.

An Ancient Protein Balances Gene Activity And Silences Foreign DNA In Bacteria

Compared to humans, bacteria have a much tidier genome. The tiny microorganisms pack their genes closely together, and don't carry around a lot of extraneous DNA, so-called junk DNA that fills in the gaps between genes. Some 90 percent of the complete genome sequence of the bacteria E. coli contains sequences of DNA that code for protein, while 90 percent of the human genome is non--coding junk DNA.

Energy in Motion

Weakness Identified In Anthrax Bacteria

MIT and New York University researchers have identified a weakness in the defenses of the anthrax bacterium that could be exploited to produce new antibiotics.

Key Anthrax Virulence Factor Discovered

Researchers have discovered how the anthrax bacterium protects itself from the immune system's biochemical assault. The results reveal not only a novel aspect of anthrax virulence, they also suggest a new target, known as bacterial nitric oxide synthase (bNOS), for fighting the pathogen, said study leader Evgeny Nudler, a professor of biochemistry at the New York University School of Medicine.

F1000 Evaluation

Dogma tells us that phagocytic cells make nitric oxide (NO) as one of several agents that kill invading pathogens. It is therefore surprising and paradoxical to discover in this paper that the bacterial NO synthase of Bacillus anthracis is a virulence factor, and that NO synthesis by the pathogen protects against macrophage killing. The suggested explanation is that NO …

Team IDs Weakness In Anthrax Bacteria

MIT and New York University researchers have identified a weakness in the defenses of the anthrax bacterium that could be exploited to produce new antibiotics. The researchers found that nitric oxide (NO) is a critical part of Bacillus anthracis's defense against the immune response launched by cells infected with the bacterium. Anthrax bacteria that cannot produce NO succumb to the immune system's attack.

No way out for anthrax?

Nitric oxide (NO), a chemical “weapon” produced by phagocytic cells of the immune system (macrophages), is part of the first wave of defense against invading pathogens such as Bacillus anthracis, the anthrax bacterium. With the aid of an intracellular fluorescent sensor for the chemical, however, Konstantin Shatalin et al. have found that NO may actually help the bacterium evade the immune system and protect it from attack.

2006 Pioneer Award Recipients

Evgeny Nudler, Ph.D., is a professor of biochemistry at the New York University School of Medicine. He received a Ph.D. in biochemistry in 1995 from the Institute of Molecular Genetics in Moscow, Russia. Nudler has done pioneering studies in various biological fields. His original work on transcription explained how RNA polymerase moves and recognizes pausing and termination signals in DNA and RNA. His studies on bacterial gene regulation led to the discovery of riboswitches (metabolite-sensing RNA) that control more than 3 percent of all bacterial genes. More recently, his group uncovered key regulators of the heat shock response in eukaryotic cells. Nudler has also made important contributions in the area of nitric oxide biochemistry in both animal and bacterial systems. He is using his Pioneer Award to develop conceptually new approaches to treat and prevent infectious diseases. Among Nudler’s honors are a Searle Scholar Award and an Edward Mallinckrodt, Jr. Foundation Award.

The logic of sharing

By implementing a systematic chromatin immunoprecipitation-microarray (ChIP-chip) analysis of the heat-shock σ-factor regulon (σ32) of Escherchia coli, Wade et al. reveal the surprising finding that there is functional overlap between σ factors.Sigma factors confer specificity on the bacterial RNA polymerase (RNAP), directing this enzyme to promoter sequences, positioning the RNAP at the promoter and effecting local unwinding of the DNA duplex near to the transcription start site.

F1000 Evaluation

By identifying binding sites for sigma-32-containing RNA polymerase in the chromosome of Escherichia coli by ChIP-Chip analysis, this paper presents a comprehensive definition of the sigma-32 heat shock regulon. Surprisingly, a large fraction of sigma-32 or sigma-E controlled promoters are also recognized by sigma-70-containing RNA polymerase, with even the same transcriptional start sites being used by the two holoenzymes.

Biochemistry

5th edition

A ratchet mechanism of transcription elongation and its control.

This article revolutionizes our understanding of the catalytic mechanism of multisubunit RNA polymerases by showing, using elegant biochemical experiments, that transcript elongation operates through a complex ratchet mechanism.

Machinations of a Maxwellian Demon

The mechanisms by which RNA polymerase moves along DNA during elongation have been difficult to determine experimentally. In this issue of Cell, Bar-Nahum et al. (2005) show that back and forth sliding of RNA polymerase on DNA may be coupled to bending of an α helix, which can alternately occlude and expose the NTP binding site. Transcription factors can regulate elongation by modulating this bending motion.

How RNA polymerase moves

Investigators may have uncovered the general mechanism that governs RNA polymerase movement, they report in the January 28 issue of Cell. The finding "provides a framework for understanding how numerous external regulatory signals converge to change the properties of the RNA polymerase active site," co-author Evgeny Nudler of New York University told The Scientist.

Issue highlight

The development of blood substitutes originally focused on heme-based compounds; however, this class of agents was problematic, in part because of their tendency to degrade nitric oxide (NO), an important endothelial product that prevents vasospasm and thrombosis. In the search for blood substitutes, perfluorocarbons recently have emerged as a promising class of compounds, largely as a result of their transport capacity for both oxygen and carbon dioxide. Rafikova and colleagues report in this issue of Circulation that perfluorocarbons offer the additional advantage of transporting NO and preserving its actions in the bloodstream

Molecular Biology (2004 3rd edition)

Third edition

Transcription through the roadblocks: the role of RNA polymerase cooperation.

This paper provides evidence that tandemly transcribing RNA polymerases cooperate to increase the overall efficiency of elongation.

Genes VIII

For courses in Molecular Biology, Molecular Genetics, and Gene Regulation. Two decades ago Benjamin Lewin's Genes revolutionized the teaching of molecular biology and molecular genetics by introducing a unified approach to bacteria and higher organisms. Genes has remained at the cutting edge of molecular biology, covering gene structure, organization, and expression. Originally the text opened with the genetic code and worked toward genome structure. Genes VIII changed the approach to begin with the sequence of the human and other genomes and starts with complete coverage of recent advances in genomics. The coverage of genomics is then integrated throughout the text. In striving to maintain currency, the new edition has updated coverage on genome organization, DNA replication, gene regulation and many other new topics.

ASM News

ASM News 70 (3) 113-114

The riboswitch-mediated control of sulfur metabolism in bacteria.

A direct experiment demonstrating, in an in vitro reaction with purified components, the action of a "riboswitch", i.e., the element on the nascent RNA transcript that controls a biological process by directly sensing the effector compound in the environment.

Genes VIII

For courses in Molecular Biology, Molecular Genetics, and Gene Regulation. Two decades ago Benjamin Lewin's Genes revolutionized the teaching of molecular biology and molecular genetics by introducing a unified approach to bacteria and higher organisms. Genes has remained at the cutting edge of molecular biology, covering gene structure, organization, and expression. Originally the text opened with the genetic code and worked toward genome structure. Genes VIII changed the approach to begin with the sequence of the human and other genomes and starts with complete coverage of recent advances in genomics. The coverage of genomics is then integrated throughout the text. In striving to maintain currency, the new edition has updated coverage on genome organization, DNA replication, gene regulation and many other new topics.

Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria.

Reports that formation of a specific complex between thiamin and riboflavin, and a conserved leader region of mRNA coding for thiamin and riboflavin biosynthetic factors, leads to a novel transcriptional regulatory mechanism.

Gene regulation: Small but perfectly ... regulating

One way for bacteria to modulate their gene expression is by attenuation — by which structural changes in the 5' leader of a transcript bring about transcription termination of downstream genes in the same operon. In most cases, a ribosome, an RNA binding protein or an uncharged tRNA can alter RNA structure so that the so-called terminator loop doesn't form; instead, the alternative structure (referred to as the antiterminator) allows transcription to proceed. Now, Mironov et al. uncover a new mechanism of attenuation. They show that, in Bacillus, some small molecules can regulate their own transcription by interacting directly with specific sequences on RNAs that are transcribed from the operon to which they belong.

Take Your Vitamins with a Pinch of RNA

RNA “aptamers” capable of binding and discriminating among structurally related small molecules can be concocted in the laboratory. Two groups have now discovered that conserved domains in the 5′ ends of some mRNAs bind specific metabolites and respond by changing their shape in biologically useful ways, demonstrating that aptamers also are present in the natural world.

Isolation and characterization of sigma(70)-retaining transcription elongation complexes from Escherichia coli.

Contrary to the 'sigma cycle' model of transcription initiation, this paper demonstrates that a significant fraction of the RNA polymerase in Escherichia coli retain sigma-70 during the elongation cycle and that this fraction reaches its maximum upon entry of cells into stationary phase.

Sigma Holds On

Many decades of work have provided details of the molecular mechanism and machinery needed for prokaryotic gene expression. Bacterial genes are transcribed by the RNA polymerase enzyme, which associates with a sigma subunit during transcription initiation. Afterwards, the sigma subunit is released from the polymerase and an elongation factor, NusA, binds. NusA remains bound to the polymerase throughout transcription elongation and termination and is then removed to allow sigma to bind once again for transcription re-initiation. This is termed the “sigma cycle.”

Molecular Biology (1999 First Edition)

First edition

Searle Scholars Program