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Genome review [Letter]
Nudler, E
ISI:000188888600003
ISSN: 0036-8733
CID: 42501
The riboswitch control of bacterial metabolism
Nudler, Evgeny; Mironov, Alexander S
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
PMID: 14729327
ISSN: 0968-0004
CID: 42616
Transcription through the roadblocks: the role of RNA polymerase cooperation
Epshtein, Vitaly; Toulme, Francine; Rahmouni, A Rachid; Borukhov, Sergei; Nudler, Evgeny
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
PMCID:212720
PMID: 12970184
ISSN: 0261-4189
CID: 48117
Cooperation between RNA polymerase molecules in transcription elongation
Epshtein, Vitaly; Nudler, Evgeny
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
PMID: 12730602
ISSN: 1095-9203
CID: 48119
The riboswitch-mediated control of sulfur metabolism in bacteria
Epshtein, Vitaly; Mironov, Alexander S; Nudler, Evgeny
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
PMCID:154296
PMID: 12702767
ISSN: 0027-8424
CID: 48120
RNA polymerase holoenzyme: structure, function and biological implications
Borukhov, Sergei; Nudler, Evgeny
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
PMID: 12732296
ISSN: 1369-5274
CID: 48118
Analysis of the intrinsic transcription termination mechanism and its control
Nudler, Evgeny; Gusarov, Ivan
PMID: 14712715
ISSN: 0076-6879
CID: 46280
Characterization of protein-nucleic acid interactions that are required for transcription processivity
Nudler, Evgeny; Avetissova, Ekaterina; Korzheva, Nataliya; Mustaev, Arkady
PMID: 14712700
ISSN: 0076-6879
CID: 46281
Methods of walking with the RNA polymerase
Nudler, Evgeny; Gusarov, Ivan; Bar-Nahum, Gil
PMID: 14712698
ISSN: 0076-6879
CID: 46282
Template switching by RNA polymerase II in vivo. Evidence and implications from a retroviral system
Kandel, Eugene S; Nudler, Evgeny
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
PMID: 12504023
ISSN: 1097-2765
CID: 48121