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mRNA Stability and Gene Expression02:51

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Cis-acting Elements in mRNA stability and Gene Expression
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Coding regions affect mRNA stability in human cells.

Ashrut Narula1,2,3, James Ellis2,3, J Matthew Taliaferro4

  • 1Program in Molecular Medicine, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.

RNA (New York, N.Y.)
|September 19, 2019
PubMed
Summary
This summary is machine-generated.

In humans, codon usage influences messenger RNA (mRNA) stability. Slow translation of specific codons increases mRNA decay, linking decoding speed to gene expression regulation.

Keywords:
codonsmRNA stabilitypost-transcriptional regulationtranslation elongation

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Area of Science:

  • Molecular Biology
  • Genetics
  • Gene Expression Regulation

Background:

  • Coding regions are increasingly recognized for their role in regulating mRNA stability.
  • In model organisms, differences in transfer RNA (tRNA) abundance lead to varied codon translation speeds, impacting mRNA decay.

Purpose of the Study:

  • To investigate whether coding regions influence mRNA stability in humans.
  • To determine the mechanisms by which open reading frames (ORFs) affect transcript stability in the human genome.

Main Methods:

  • Utilized the human ORFeome collection to isolate RNA stability effects attributed to coding regions.
  • Analyzed open reading frame (ORF) characteristics and codon usage in relation to mRNA stability.
  • Measured A-site dwell times for instability-associated codons.

Main Results:

  • Many ORF characteristics (e.g., length, secondary structure) do not explain alterations in mRNA stability.
  • mRNA stability is influenced by the translation process within the ORF.
  • Codon usage significantly correlates with the impact of ORFs on transcript stability.
  • Instability-associated codons exhibit longer A-site dwell times, indicating slower translation.

Conclusions:

  • Codon usage impacts mRNA stability in humans by altering translation speed.
  • A direct link between codon decoding speed (elongation speed) and mRNA decay is proposed for humans.
  • This suggests a novel mechanism for gene expression regulation through codon-optimized translation impacting mRNA stability.