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Evgeny Nudler

Publications and source records attributed to Evgeny Nudler.

12 recordsLinked to original sources
PubMed2004

The riboswitch control of bacterial metabolism.

Aptamers are artificial nucleic acids that selectively bind small molecules. In the past two years, it has become clear that nature has already devised its own aptamers that play important regulatory roles. RNA sensors have been discovered in both Gram-positive and Gram-negative bacteria that function as molecular switches in response to direct binding of structurally diverse metabolites. These natural RNA aptamers, called 'riboswitches', are imbedded in the leader sequences of numerous metabolic genes. Riboswitches are able to repress or activate their cognate genes at both transcriptional and translational levels. Here, we summarize the recent progress in the identification and characterization of riboswitches and discuss their evolution and distribution.

Bacteria↗
PubMed2003

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

During transcription, cellular RNA polymerases (RNAP) have to deal with numerous potential roadblocks imposed by various DNA binding proteins. Many such proteins partially or completely interrupt a single round of RNA chain elongation in vitro. Here we demonstrate that Escherichia coli RNAP can effectively read through the site-specific DNA-binding proteins in vitro and in vivo if more than one RNAP molecule is allowed to initiate from the same promoter. The anti-roadblock activity of the trailing RNAP does not require transcript cleavage activity but relies on forward translocation of roadblocked complexes. These results support a cooperation model of transcription whereby RNAP molecules behave as 'partners' helping one another to traverse intrinsic and extrinsic obstacles.

Base Sequence↗
PubMed2003

Cooperation between RNA polymerase molecules in transcription elongation.

Transcription elongation is responsible for rapid synthesis of RNA chains of thousands of nucleotides in vivo. In contrast, a single round of transcription performed in vitro is frequently interrupted by pauses and arrests that drastically reduce the elongation rate and the yield of the full-length transcript. Here we demonstrate that most transcriptional delays disappear if more than one RNA polymerase (RNAP) molecule initiates from the same promoter. Anti-arrest and anti-pause effects of trailing RNAP are due to forward translocation of leading (backtracked) complexes. Such cooperation between RNAP molecules links the rate of elongation to the rate of initiation and explains why elongation is still fast and processive in vivo even without anti-arrest factors.

Adenosine Triphosphate↗
PubMed2003

The riboswitch-mediated control of sulfur metabolism in bacteria.

Many operons in Gram-positive bacteria that are involved in methionine (Met) and cysteine (Cys) biosynthesis possess an evolutionarily conserved regulatory leader sequence (S-box) that positively controls these genes in response to methionine starvation. Here, we demonstrate that a feed-back regulation mechanism utilizes S-adenosyl-methionine as an effector. S-adenosyl-methionine directly and specifically binds to the nascent S-box RNA, causing an intrinsic terminator to form and interrupt transcription prematurely. The S-box leader RNA thus expands the family of newly discovered riboswitches, i.e., natural regulatory RNA aptamers that seem to sense small molecules ranging from amino acid derivatives to vitamins.

Base Sequence↗
PubMed2003

RNA polymerase holoenzyme: structure, function and biological implications.

The past three years have marked the breakthrough in our understanding of the structural and functional organization of RNA polymerase. The latest major advance was the high-resolution structures of bacterial RNA polymerase holoenzyme and the holoenzyme in complex with promoter DNA. Together with an array of genetic, biochemical and biophysical data accumulated to date, the structures provide a comprehensive view of dynamic interactions between the major components of transcription machinery during the early stages of the transcription cycle. They include the binding of sigma factor to the core enzyme, and the recognition of promoter sequences and DNA melting by holoenzyme, transcription initiation and promoter clearance.

Bacteria↗
PubMed2002

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

Thiamin and riboflavin are precursors of essential coenzymes-thiamin pyrophosphate (TPP) and flavin mononucleotide (FMN)/flavin adenine dinucleotide (FAD), respectively. In Bacillus spp, genes responsible for thiamin and riboflavin biosynthesis are organized in tightly controllable operons. Here, we demonstrate that the feedback regulation of riboflavin and thiamin genes relies on a novel transcription attenuation mechanism. A unique feature of this mechanism is the formation of specific complexes between a conserved leader region of the cognate RNA and FMN or TPP. In each case, the complex allows the termination hairpin to form and interrupt transcription prematurely. Thus, sensing small molecules by nascent RNA controls transcription elongation of riboflavin and thiamin operons and possibly other bacterial operons as well.

Bacillus subtilis↗
PubMed2002

Catalysis of S-nitrosothiols formation by serum albumin: the mechanism and implication in vascular control.

Nitric oxide (NO(.)) is a short-lived physiological messenger. Its various biological activities can be preserved in a more stable form of S-nitrosothiols (RS-NO). Here we demonstrate that at physiological NO(.) concentrations, plasma albumin becomes saturated with NO(.) and accelerates formation of low-molecular-weight (LMW) RS-NO in vitro and in vivo. The mechanism involves micellar catalysis of NO(.) oxidation in the albumin hydrophobic core and specific transfer of NO(+) to LMW thiols. Albumin-mediated S-nitrosylation and its vasodilatory effect directly depend on the concentration of circulating LMW thiols. Results suggest that the hydrophobic phase formed by albumin serves as a major reservoir of NO(.) and its reactive oxides and controls the dynamics of NO(.)-dependant processes in the vasculature.

Albumins↗
PubMed2002

Template switching by RNA polymerase II in vivo. Evidence and implications from a retroviral system.

Transfection of retrovirus packaging cells with linear DNA from a retroviral vector missing the 3' long terminal repeat (3' LTR) results in production of infectious virus. Analysis of the newly formed proviruses indicates that restoration of the 3' LTR sequences necessary for reverse transcription and integration occurred due to end-to-end template switching by mammalian RNA polymerase II (RNAP II) in the packaging cells. These observations argue that RNAP II can utilize double-strand breaks and gaps in DNA to generate "recombinant" transcripts in vivo and suggest a mechanism for mutation and recombination of retroviruses.

Animals↗
PubMed2002

Transcription termination and anti-termination in E. coli.

Transcription termination in Escherichia coli is controlled by many factors. The sequence of the DNA template, the structure of the transcript, and the actions of auxiliary proteins all play a role in determining the efficiency of the process. Termination is regulated and can be enhanced or suppressed by host and phage proteins. This complex reaction is rapidly yielding to biochemical and structural analysis of the interacting factors. Below we review and attempt to unify into basic principles the remarkable recent progress in understanding transcription termination and anti-termination.

Bacteriophages↗