The MRNA Degradation Factor Xrn1 Regulates Transcription Elongation in Parallel to Ccr4

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2019 Aug 9

PMID 31392315

Citations 15

Authors

Victoria Begley

Daniel Corzo

Antonio Jordan-Pla

Abel Cuevas-Bermudez

Lola de Miguel-Jimenez

David Perez-Aguado

Mercedes Machuca-Ostos

Francisco Navarro

Maria Jose Chavez

Jose E Perez-Ortin

Sebastian Chavez

Affiliations

Soon will be listed here.

Abstract

Co-transcriptional imprinting of mRNA by Rpb4 and Rpb7 subunits of RNA polymerase II (RNAPII) and by the Ccr4-Not complex conditions its post-transcriptional fate. In turn, mRNA degradation factors like Xrn1 are able to influence RNAPII-dependent transcription, making a feedback loop that contributes to mRNA homeostasis. In this work, we have used repressible yeast GAL genes to perform accurate measurements of transcription and mRNA degradation in a set of mutants. This genetic analysis uncovered a link from mRNA decay to transcription elongation. We combined this experimental approach with computational multi-agent modelling and tested different possibilities of Xrn1 and Ccr4 action in gene transcription. This double strategy brought us to conclude that both Xrn1-decaysome and Ccr4-Not regulate RNAPII elongation, and that they do it in parallel. We validated this conclusion measuring TFIIS genome-wide recruitment to elongating RNAPII. We found that xrn1Δ and ccr4Δ exhibited very different patterns of TFIIS versus RNAPII occupancy, which confirmed their distinct role in controlling transcription elongation. We also found that the relative influence of Xrn1 and Ccr4 is different in the genes encoding ribosomal proteins as compared to the rest of the genome.

Citing Articles

The zinc-finger transcription factor Sfp1 imprints specific classes of mRNAs and links their synthesis to cytoplasmic decay.

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Homeostasis of mRNA concentrations through coupling transcription, export, and degradation.

Wang Q, Lin J iScience. 2024; 27(8):110531.

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Disruption of the Mammalian Ccr4-Not Complex Contributes to Transcription-Mediated Genome Instability.

Chalabi Hagkarim N, Hajkarim M, Suzuki T, Fujiwara T, Winkler G, Stewart G Cells. 2023; 12(14).

PMID: 37508532 PMC: 10378556. DOI: 10.3390/cells12141868.

Enhanced gene regulation by cooperation between mRNA decay and gene transcription.

Garcia-Martinez J, Singh A, Medina D, Chavez S, Perez-Ortin J Biochim Biophys Acta Gene Regul Mech. 2023; 1866(2):194910.

PMID: 36731791 PMC: 10663100. DOI: 10.1016/j.bbagrm.2023.194910.

RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and a novel mRNA decay pathway.

Chattopadhyay S, Garcia-Martinez J, Haimovich G, Fischer J, Khwaja A, Barkai O Nat Commun. 2022; 13(1):7184.

PMID: 36418294 PMC: 9684461. DOI: 10.1038/s41467-022-34417-z.

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