Transcription fidelity and its roles in the cell

Abstract

HighlightsThe Trigger Loop is one of the major determinants of transcription fidelity.Intrinsic proofreading occurs via transcript-assisted cleavage.Factor-assisted proofreading takes place via exchange of RNAP active centres.Misincorporation is a major source of transcription pausing.Another role of fidelity is the prevention of conflicts with other cellular processes.

Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases

“…Fidelity of RNA synthesis is an estimation of the frequency of non-Watson-Crick base pairs formed during RNA chain growth driven by RNA polymerases. The same phenomenon is described for DNA polymerases [ 1 , 2 , 3 , 4 , 5 ]. Hence, fidelity of viral RNA synthesis refers to the appearance of non-Watson-Crick base pairs during viral RNA-dependent RNA polymerase (RdRp)-mediated RNA chain growth.…”

“…In cells there is a plethora of naturally-occurring nucleotide analogues, which must be selected against in order to produce bona fide viral RNA, and an infectious genome in fine. To achieve selectivity, RNA and DNA polymerases in general have evolved selective “gates” and molecular sensors in their active sites to precisely probe the correctness of the base, the absence or presence of a hydroxyl group at the 2′ position of the ribose moiety of nucleoside triphosphates, and the presence of the triphosphate [ 2 , 20 , 21 , 22 , 23 ]. The need for a correct ribose moiety can be overcome in some instances, though: chemists have proposed ribose modifications to trick viral polymerases.…”

Errors during Gene Expression: Single-Cell Heterogeneity, Stress Resistance, and Microbe-Host Interactions

“…Despite the clear role that transcriptional accuracy must play in gene expression, transcriptional error rates have been estimated to reach 10 −5 errors per nucleotide ( 2 ). Traditionally, transcriptional error rates are determined using in vitro transcription by RNA polymerases or in vivo reporters ( 6 ). Several recent studies have used high-throughput RNA sequencing with improved fidelity during cDNA synthesis and sequencing to determine global transcriptional error rates in multiple bacteria ( 7 ).…”

Integrated-structure emergence and its mechanistic explanation

“…Another clear example of such cyclic causal relations is the correction of transcription errors. Indeed, it is now known that transcription errors are often successfully edited by quality control mechanisms, involving a variety of proofreading mechanisms (e.g., Gamba & Zenkin 2018). Furthermore, such "quality control mechanisms do not just remove errors; rather, they recognise misincorporations, remove them and insert correct nucleotides".…”