Coding regions affect mRNA stability in human cells

A new paradigm has emerged that coding regions can regulate mRNA stability in model organisms. Here, due to differences in cognate tRNA abundance, synonymous codons are translated at different speeds, and slow codons then stimulate mRNA decay. To ask if this phenomenon also occurs in humans, we isol...

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Bibliographic Details
Published in:RNA (Cambridge) 2019-12, Vol.25 (12), p.1751-1764
Main Authors: Narula, Ashrut, Ellis, James, Taliaferro, J Matthew, Rissland, Olivia S
Format: Article
Language:English
Subjects:
Cell Line
Codon - genetics
Codons
Goats
HEK293 Cells
Humans
mRNA stability
mRNA turnover
Open reading frames
Open Reading Frames - genetics
Protein Biosynthesis - genetics
Protein structure
Protein Structure, Secondary - genetics
RNA Stability - genetics
RNA, Messenger - genetics
RNA, Transfer - genetics
Secondary structure
Transcription
tRNA
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Summary:A new paradigm has emerged that coding regions can regulate mRNA stability in model organisms. Here, due to differences in cognate tRNA abundance, synonymous codons are translated at different speeds, and slow codons then stimulate mRNA decay. To ask if this phenomenon also occurs in humans, we isolated RNA stability effects due to coding regions using the human ORFeome collection. We find that many open reading frame (ORF) characteristics, such as length and secondary structure, fail to provide explanations for how coding regions alter mRNA stability, and, instead, that the ORF relies on translation to impact mRNA stability. Consistent with what has been seen in other organisms, codon use is related to the effects of ORFs on transcript stability. Importantly, we found instability-associated codons have longer A-site dwell times, suggesting for the first time in humans a connection between elongation speed and mRNA decay. Thus, we propose that codon usage alters decoding speeds and so affects human mRNA stability.
ISSN:1355-8382
1469-9001
DOI:10.1261/rna.073239.119