Post‐Transcriptional Regulation of Gene Expression and the Intricate Life of Eukaryotic mRNAs

Wiley Interdisciplinary Reviews - RNA, Год журнала: 2025, Номер 16(2)

Опубликована: Март 1, 2025

In recent years, there has been a growing appreciation for how regulatory events that occur either co- or post-transcriptionally contribute to the control of gene expression. Messenger RNAs (mRNAs) are extensively regulated throughout their metabolism in precise spatiotemporal manner requires sophisticated molecular mechanisms cell-type-specific expression, which dictates cell function. Moreover, dysfunction at any these steps can result variety human diseases, including cancers, muscular atrophies, and neurological diseases. This review summarizes central dogma biology, focusing on post-transcriptional regulation

Язык: Английский

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Widespread epistasis shapes RNA Polymerase II active site function and evolution

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Фев. 28, 2023

ABSTRACT Multi-subunit RNA Polymerases (msRNAPs) are responsible for transcription in all kingdoms of life. These enzymes rely on dynamic, highly conserved active site domains such as the so-called “trigger loop” (TL) to accomplish steps cycle. Mutations polymerase II (Pol II) TL confer a spectrum biochemical and genetic phenotypes that suggest two main classes, which decrease or increase catalysis other nucleotide addition cycle (NAC) events. The Pol relies networks residue interactions function mutations likely perturb these ways may alter mechanisms. We have undertaken structural genetics approach reveal within surrounding – determining its “interaction landscape” by deep mutational scanning Saccharomyces cerevisiae II. This analysis reveals connections between residues domains, demonstrating is tightly coupled specific enzyme context.

Язык: Английский

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Higher-order epistasis within Pol II trigger loop haplotypes

Genetics, Год журнала: 2024, Номер unknown

Опубликована: Окт. 24, 2024

Abstract RNA polymerase II (Pol II) has a highly conserved domain, the trigger loop (TL), that controls transcription fidelity and speed. We previously probed pairwise genetic interactions between residues within surrounding TL for purpose of understanding functional to understand how individual mutants might alter function. identified widespread incompatibility TLs different species when placed in Saccharomyces cerevisiae Pol context, indicating species-specific otherwise their surroundings. These represent epistasis rest II. sought why certain sequences are incompatible with S. dissect nature multiply substituted as window on higher-order this system. both positive negative residue example haplotypes. Intricate formed by was sometimes only apparent from analysis intermediate genotypes, emphasizing complexity epistatic interactions. Furthermore, we distinguished substitutions distinct classes patterns, suggesting specific potentially influence evolution. Our examples complex suggest possible pathways facilitate

Язык: Английский

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Controlling Transcription Elongation and Termination: More Than a Means to An End

Journal of Molecular Biology, Год журнала: 2024, Номер unknown, С. 168886 - 168886

Опубликована: Ноя. 1, 2024

Язык: Английский

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