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High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
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High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes

Published on: March 3, 2015

An mRNA surveillance mechanism that eliminates transcripts lacking termination codons

Pamela A Frischmeyer1, Ambro van Hoof, Kathryn O'Donnell

  • 1Institute for Genetic Medicine, Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Science (New York, N.Y.)
|March 23, 2002
PubMed

Insights

Messenger RNAs (mRNAs) lacking stop codons are rapidly degraded by a translation-dependent pathway distinct from nonsense-mediated mRNA decay (NMD). This nonstop mRNA decay mechanism is conserved in mammals and regulates gene expression.

Area of Science:

  • Molecular Biology
  • Gene Expression Regulation
  • RNA Metabolism

Background:

  • Translation quality control is crucial for cellular health.
  • Nonsense-mediated mRNA decay (NMD) degrades transcripts with premature termination codons (PTCs).
  • The fate of mRNAs lacking any termination codons was previously unclear.

Purpose of the Study:

  • To investigate the decay mechanism of nonstop mRNAs.
  • To determine if nonstop mRNA decay is related to known mRNA degradation pathways.
  • To identify physiological sources and conservation of nonstop mRNA decay.

Main Methods:

  • Utilized yeast as a model organism.
  • Investigated mRNA decay pathways through genetic and biochemical approaches.
  • Examined nonstop mRNA decay in mammalian cells.

Main Results:

  • mRNAs lacking termination codons (nonstop mRNAs) are rapidly degraded in yeast.
  • Nonstop mRNA decay requires translation but is mechanistically distinct from NMD and other major decay pathways.
  • Nonstop transcripts are generated from multiple physiological sources and their accelerated decay is conserved in mammalian cells.

Conclusions:

  • A novel translation-dependent mRNA decay pathway, termed nonstop decay, targets mRNAs lacking termination signals.
  • Nonstop decay is initiated when ribosomes reach the 3' end of the mRNA.
  • This pathway plays a significant role in regulating the expression of mRNAs that fail to terminate translation properly.

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