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Analysis of RNA Processing Reactions Using Cell Free Systems: 3' End Cleavage of Pre-mRNA Substrates in vitro
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Published on: May 3, 2014

Quality control of mRNA 3'-end processing is linked to the nuclear exosome

P Hilleren1, T McCarthy, M Rosbash

  • 1Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA. hilleren@u.arizona.edu

Nature
|October 5, 2001
PubMed

Insights

Messenger RNA (mRNA) processing and export are linked for quality control. The nuclear exosome, with Rrp6p, acts as a checkpoint for proper mRNA 3'-end formation, retaining faulty transcripts.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Messenger RNA (mRNA) metabolism involves nuclear pre-mRNA processing coupled to cytoplasmic export for quality control.
  • In Saccharomyces cerevisiae, defective mRNA nuclear export leads to hyperadenylation and retention of transcripts at transcription sites.
  • This suggests a coupling mechanism between polyadenylation and nuclear export involving release from transcription sites.

Purpose of the Study:

  • To investigate the role of 3'-end processing in mRNA nuclear export and retention.
  • To identify factors involved in the retention of improperly processed mRNAs at transcription sites.
  • To elucidate the function of the nuclear exosome in mRNA quality control.

Main Methods:

  • Analysis of mRNA processing and localization in Saccharomyces cerevisiae.
  • Investigating the role of Rrp6p and the nuclear exosome in mRNA metabolism.
  • Comparing mRNA retention in wild-type and exosome mutant strains.

Main Results:

  • Transcripts lacking a poly(A) tail are retained at transcription sites, similar to hyperadenylated transcripts.
  • This retention mechanism requires the protein Rrp6p and the nuclear exosome.
  • In exosome mutants, both hypo- and hyperadenylated mRNAs are released and translated, indicating a failure in quality control.

Conclusions:

  • The nuclear exosome, including Rrp6p, plays a crucial role in retaining improperly 3'-end processed mRNAs at transcription sites.
  • The exosome acts as a checkpoint monitoring mRNA 3'-end formation, ensuring proper processing before export.
  • Dysfunction of the exosome leads to the release and potential translation of aberrant mRNAs, compromising cellular quality control.

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