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… 

RNA polymerase fidelity and transcriptional proofreading.

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 the

olecular basis of transcriptional fidelity and DNA lesion-induced ranscriptional 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 of controlling Pol II transcriptionalidelity.

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.

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.

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.

Research articleStepwise mechanism for transcription fidelity

A flexible domain of the RNA polymerase active centre, the Trigger Loop, was shown to play an important role in this process, but the mechanisms of this participation are still unclear.

Structural basis of transcription elongation.

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.



Fidelity of RNA polymerase II transcription controlled by elongation factor TFIIS.

  • C. JeonK. Agarwal
  • Biology
    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.

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.

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.

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.

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.