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Quality control of transcription start site selection by nonsense-mediated-mRNA decay

Christophe Malabat1, Frank Feuerbach1, Laurence Ma2

  • 1Institut Pasteur, UMR3525, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Paris, France.

Elife
|April 24, 2015
PubMed

Insights

Nonsense-mediated mRNA decay (NMD) degrades pervasive transcripts, acting as a crucial RNA quality control. This pathway removes spurious transcripts, including those with upstream open reading frames (uORFs), ensuring genomic integrity.

Area of Science:

  • Molecular Biology
  • Genetics
  • RNA Biology

Background:

  • Nonsense-mediated mRNA decay (NMD) is a key translation-dependent RNA quality control pathway.
  • NMD targets aberrant transcripts, including those with premature stop codons or upstream open reading frames (uORFs).

Purpose of the Study:

  • To investigate the role of NMD in degrading pervasive transcripts in Saccharomyces cerevisiae.
  • To analyze the impact of transcription start site (TSS) selection on NMD-sensitive transcript isoforms.

Main Methods:

  • Transcription start site (TSS) analysis in Saccharomyces cerevisiae cells deficient for RNA degradation pathways.
  • Analysis of pervasive transcripts and NMD-sensitive isoforms.

Main Results:

  • Approximately half of pervasive transcripts are degraded by NMD, serving as a nuclear RNA surveillance mechanism.
  • Low specificity of RNA polymerase II TSS selection generates NMD-sensitive isoforms for 47% of genes, often containing uORFs.
  • A bias against in-frame ATGs and depletion of N-terminal methionines suggest these isoforms constrain genomic sequences.

Conclusions:

  • NMD plays a significant role in clearing spurious transcripts that escape nuclear degradation.
  • Transcriptional regulation and NMD collaborate to maintain RNA quality and influence genomic sequence evolution.
Keywords:
RNA quality controlS. cerevisiaechromosomesevolutionary biologygenesgenomicsnon-coding RNAsnon-sense mediated mRNA decaynuclear RNA degradationtranscription initiation

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