Transcript-Assisted Transcriptional Proofreading

  title={Transcript-Assisted Transcriptional Proofreading},
  author={Nikolay Zenkin and Yulia Yuzenkova and Konstantin V. Severinov},
  pages={518 - 520}
Fidelity of template-dependent nucleic acid synthesis is the main determinant of stable heredity and error-free gene expression. The mechanism (or mechanisms) ensuring fidelity of transcription by DNA-dependent RNA polymerases (RNAPs) is not fully understood. Here, we show that the 3′ end–proximal nucleotide of the nascent transcript stimulates hydrolysis of the penultimate phosphodiester bond by providing active groups and coordination bonds to the RNAP active center. This stimulation is much… Expand
RNA polymerase fidelity and transcriptional proofreading.
New functional and structural studies now suggest how RNAPs select the correct nucleoside triphosphate (NTP) substrate to prevent transcription errors, and how the enzymes detect and remove a misincorporated nucleotide during proofreading. Expand
Transcriptional accuracy modeling suggests two-step proofreading by RNA polymerase
Abstract We suggest a novel two-step proofreading mechanism with two sequential rounds of proofreading selection in mRNA transcription. It is based on the previous experimental observations that theExpand
olecular basis of transcriptional fidelity and DNA lesion-induced ranscriptional mutagenesis
Maintaining high transcriptional fidelity is essential for life. Some DNA lesions lead to significant changes in transcriptional fidelity. In this review, we will summarize recent progress towardsExpand
Control of Transcriptional Fidelity by Active Center Tuning as Derived from RNA Polymerase Endonuclease Reaction*
The unified mechanism for RNA synthesis and degradation by RNA polymerase predicts that ACT also executes NTP selection thereby contributing to high transcription fidelity. Expand
Molecular basis of transcriptional fidelity and DNA lesion-induced transcriptional mutagenesis.
This review will summarize recent progress towards understanding the molecular basis of RNA polymerase II (Pol II) transcriptional fidelity and DNA lesion-induced transcriptional mutagenesis, and focus on the three key checkpoint steps. Expand
Central role of the RNA polymerase trigger loop in intrinsic RNA hydrolysis
It is shown that the invariant histidine (β′ His1242) of the TL is essential for hydrolysis/proofreading and participates in the reaction in two distinct ways: by positioning the 3′ end nucleotide of the transcript that assists catalysis and/or by directly participating in the Reaction as a general base. Expand
Dissecting chemical interactions governing RNA polymerase II transcriptional fidelity.
This work provides the first systematic evaluation of electrostatic and steric effects in controlling Pol II transcriptional fidelity and finds that whereas hydrogen bonds between a Watson-Crick base pair of template DNA and incoming NTP are critical for efficient incorporation, they are not required for efficient transcript extension from this matched 3'-RNA end. Expand
Research articleStepwise mechanism for transcription fidelity
Background: Transcription is the first step of gene expression and is characterized by a high fidelity of RNA synthesis. During transcription, the RNA polymerase active centre discriminates againstExpand
Structural basis of transcription elongation.
These studies that elucidated EC structure and maintenance, nucleotide selection and addition, translocation, elongation inhibition, pausing and proofreading, backtracking, arrest and reactivation, processivity, DNA lesion-induced stalling, lesion bypass, and transcriptional mutagenesis are summarized. Expand
Stepwise mechanism for transcription fidelity
It is demonstrated that fidelity of transcription by multi-subunit RNA polymerases is achieved through a stepwise process and it is shown that individual steps contribute differently to discrimination against various erroneous substrates. Expand


Transcriptional Fidelity and Proofreading by RNA Polymerase II
It is demonstrated that addition of SII to a transcription reaction dramatically altered the RNA base content, reflecting the stable incorporation of more "correct" (GMP) and fewer "incorrect" (IMP) nucleotides. Expand
Fidelity of RNA polymerase II transcription controlled by elongation factor TFIIS.
  • C. Jeon, K. Agarwal
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1996
It is demonstrated that RNA polymerase II can misincorporate a nucleotide and carry out template-dependent elongation at the mispaired end and enhanced preferential cleavage of misincorporated transcripts suggests an important role for TFIIS in maintaining transcriptional fidelity. Expand
Multiple RNA polymerase conformations and GreA: control of the fidelity of transcription.
The transcription cleavage factor GreA increased the fidelity of transcription by preferential cleavage of transcripts containing misincorporated residues in the unactivated state of the elongation complex, which may prevent the formation of "dead-end" transcription complexes in vivo. Expand
Allosteric Binding of Nucleoside Triphosphates to RNA Polymerase Regulates Transcription Elongation
The regulation of transcription elongation and termination appears to be governed by the ability of RNA polymerase elongation complexes to adopt multiple conformational states; however, the factorsExpand
Transcriptional fidelity and proofreading in Archaea and implications for the mechanism of TFS‐induced RNA cleavage
Analysis of paused elongation complexes demonstrated that TFS is able to induce a cleavage resynthesis cycle in such complexes, which resulted in the accumulation of dinucleotides corresponding to the last two nucleotides of the transcript. Expand
A Ratchet Mechanism of Transcription Elongation and Its Control
A general mechanism that governs RNA polymerase (RNAP) movement and response to regulatory inputs such as pauses, terminators, and elongation factors is described. Expand
Unified two‐metal mechanism of RNA synthesis and degradation by RNA polymerase
This work proposes a unified catalytic mechanism for multisubunit RNA polymerases based on the analysis of its 3′–5′ exonuclease reaction in the context of crystal structure. Expand
Analysis of RNA chain elongation and termination by Saccharomyces cerevisiae RNA polymerase III.
Quantitative analysis of the individual steps of RNA chain elongation showed that steps of adding U and A to U-terminated RNA chains tended to be relatively slow, and to be more strongly influenced by nucleotide concentration. Expand
Mechanism of DmS-II-mediated pause suppression by Drosophila RNA polymerase II.
  • H. Guo, D. Price
  • Medicine, Biology
  • The Journal of biological chemistry
  • 1993
The results show that DmS-II is necessary and sufficient to activate nascent transcript cleavage by RNA polymerase II during transcription of a dC-tailed template, and support a model for pause suppression in which Dm S-II binds to the paused polymerase, causes one cleavage event and is then released from the complex. Expand
Structural Basis of Transcription: RNA Polymerase II at 2.8 Ångstrom Resolution
Structures of a 10-subunit yeast RNA polymerase II derived from two crystal forms at 2.8 and 3.1 angstrom resolution provide evidence for RNA exit in the vicinity of the carboxyl-terminal repeat domain, coupling synthesis to RNA processing by enzymes bound to this domain. Expand