Our most significant contributions include:
- RNA polymerase “backtracking” and “ratcheting”: In 1997 we described back- and-forth sliding of RNAP along DNA and RNA. Our group then showed that this phenomenon, which we called “backtracking”, plays the key role in controlling gene expression and is a source of genome instability. We also demonstrated that RNAP is a Brownian ratchet machine. Our findings explained in mechanistical details how RNAP translocates, how it responds to regulatory signals and factors, and how it terminates transcription.
- Riboswitches: In 2002, we described the first ligand-sensing mRNAs that regulate biosynthetic genes in B. subtilis. Simultaneously, Ron Breaker reported similar findings in E.coli. Since then dozens of riboswitches have been described in many evolutionarily distant bacteria, with counterparts in archaea, plants, fungi, and algae, where they control numerous genes.
- Eukaryotic thermosensor: In 2006 we isolated a complex composed of the translation elongation factor eEF1A1 and a novel non-coding RNA (HSR1) that is required for activation of heat shock genes in mammals. We proposed that HSR1 serves as a molecular thermosensor. We then showed that eEF1A1 orchestrates the whole process of heat shock response, from transcription activation to mRNA stabilization, transport, and translation. These findings provide a new paradigm of cellular adaptation to stress, with far-reaching clinical implications.
- Bacterial gasotransmitters: We have shown that endogenously produced gases NO and H2S protect bacteria from oxidative stress, immune attack, and numerous antibiotics. These results provide an experimental support for the emerging concept of antibiotic killing, which relies on oxidative damage, and establish NO- and H2S-producing enzymes as promising new targets for antimicrobial therapy. We further showed that NO produced by bacteria inside C. elegans diffuses into animal’s tissues where it activates a defined set of genes that protect nematodes from environmental stress and extend their lifespan.
- ppGpp couples transcription to DNA repair in E. coli. Science. 20 May 2016. 352(6288):993-6
- UvrD facilitates DNA repair by pulling RNA polymerase backwards. Nature. 16 Jan 2014. 505:372-377
- PDF | Bacterial Nitric Oxide Extends the Lifespan of C. elegans Cell. 14 Feb 2013. 152(4):818-830
- PDF | H2S: a universal defense against antibiotics in bacteria. Science. 18 Nov 2011. 334(6058):986-90
- PDF | Linking RNA polymerase backtracking to genome instability in E. coli. Cell. 19 Aug 2011. 146(4):533-43
- Cooperation between translating ribosomes and RNA polymerase in transcription elongation. Science. 23 Apr 2010. 328(5977):504-8
- An allosteric mechanism of Rho-dependent transcription termination. Nature. 14 Jan 2010. 463(7278):245-9
- Endogenous nitric oxide protects bacteria against a wide spectrum of antibiotics. Science. 11 Sep 2009. 325(5946):1380-4
- Termination factor Rho and its cofactors NusA and NusG silence foreign DNA in E. coli. Science. 16 May 2008. 320(5878):935-8
- Bacillus anthracis-derived nitric oxide is essential for pathogen virulence and survival in macrophages. Proc Natl Acad Sci U S A. 22 Jan 2008. 105(3):1009-13
- An allosteric path to transcription termination. Mol Cell. 28 Dec 2007. 28(6):991-1001
- Extensive functional overlap between sigma factors in Escherichia coli. Nat Struct Mol Biol. 01 Sep 2006. 13(9):806-14
- NO-mediated cytoprotection: instant adaptation to oxidative stress in bacteria. Proc Natl Acad Sci U S A. 27 Sep 2005. 102(39):13855-60
- A ratchet mechanism of transcription elongation and its control. Cell. 28 Jan 2005. 120(2):183-93
- Cooperation between RNA polymerase molecules in transcription elongation. Science. 02 May 2003. 300(5620):801-5
- The riboswitch-mediated control of sulfur metabolism in bacteria. Proc Natl Acad Sci U S A. 29 Apr 2003. 100(9):5052-6
- Template switching by RNA polymerase II in vivo. Evidence and implications from a retroviral system. Mol Cell. 01 Dec 2002. 10(6):1495-502
- Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria. Cell. 27 Nov 2002. 111(5):747-56
- Control of intrinsic transcription termination by N and NusA: the basic mechanisms. Cell. 16 Nov 2001. 107(4):437-49
- Isolation and characterization of sigma(70)-retaining transcription elongation complexes from Escherichia coli. Cell. 24 Aug 2001. 106(4):443-51
- The mechanism of intrinsic transcription termination. Mol Cell. 01 Apr 1999. 3(4):495-504
- Spatial organization of transcription elongation complex in Escherichia coli. Science. 17 Jul 1998. 281(5375):424-8
- The RNA-DNA hybrid maintains the register of transcription by preventing backtracking of RNA polymerase. Cell. 04 Apr 1997. 89(1):33-41