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Regulation of mature mRNA levels by RNA processing efficiency

Abstract:
Transcription and co-transcriptional processes, including pre-mRNA splicing and mRNA cleavage and polyadenylation, regulate the production of mature mRNAs. The carboxyl terminal domain (CTD) of RNA polymerase (pol) II, which comprises 52 repeats of the Tyr1Ser2Pro3Thr4Ser5Pro6Ser7 peptide, is involved in the coordination of transcription with co-transcriptional processes. The pol II CTD is dynamically modified by protein phosphorylation, which regulates recruitment of transcription and co-transcriptional factors. We have investigated whether mature mRNA levels from intron-containing protein-coding genes are related to pol II CTD phosphorylation, RNA stability, and pre-mRNA splicing and mRNA cleavage and polyadenylation efficiency. We find that genes that produce a low level of mature mRNAs are associated with relatively high phosphorylation of the pol II CTD Thr4 residue, poor RNA processing, increased chromatin association of transcripts, and shorter RNA half-life. While these poorly-processed transcripts are degraded by the nuclear RNA exosome, our results indicate that in addition to RNA half-life, chromatin association due to a low RNA processing efficiency also plays an important role in the regulation of mature mRNA levels.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1093/nargab/lqad059

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pathology Dunn School
Role:
Author
ORCID:
0000-0001-9277-9960
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pathology Dunn School
Oxford college:
Oriel College
Role:
Author
ORCID:
0000-0001-5276-9645
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pathology Dunn School
Role:
Author


More from this funder
Grant:
210641/Z/18/Z
106134/Z/14/Z


Publisher:
Oxford University Press
Journal:
NAR Genomics and Bioinformatics More from this journal
Volume:
5
Issue:
2
Article number:
lqad059
Publication date:
2023-06-09
Acceptance date:
2023-05-24
DOI:
EISSN:
2631-9268


Language:
English
Keywords:
Pubs id:
1345630
Local pid:
pubs:1345630
Deposit date:
2023-05-25

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