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Updated: Sep 20, 2025

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Human CCR4 deadenylase homolog Angel1 is a non-stop mRNA decay factor

Tim Nicholson-Shaw1, Megan E Dowdle1, Yasmeen Ajaj1

  • 1Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA.

RNA (New York, N.Y.)
|May 29, 2025
PubMed

Insights

Angel1 is identified as a key factor in non-stop mRNA decay (NSD), a pathway that degrades faulty mRNAs lacking stop codons. Its catalytic activity is crucial for this essential cellular process.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Cellular Quality Control

Background:

  • Translation elongation stalls trigger mRNA decay and nascent polypeptide degradation through quality control pathways.
  • Non-stop mRNA decay (NSD) specifically targets aberrant mRNAs lacking stop codons, often due to premature polyadenylation.

Purpose of the Study:

  • To identify novel factors involved in the non-stop mRNA decay (NSD) pathway in human cells.
  • To elucidate the biochemical role and mechanism of Angel1 in NSD.

Main Methods:

  • Biochemical assays to define the activity of Angel1, a CCR4 deadenylase homolog.
  • Cellular depletion studies using reporter mRNAs to assess Angel1's function in NSD.
  • Analysis of Angel1's association with mRNA and relevant protein complexes.

Main Results:

  • Angel1 was identified as a rate-limiting factor for NSD in human cells.
  • Angel1 associates with mRNA coding regions and proteins involved in ribosome-associated quality control and mRNA decay.
  • Depletion of Angel1 stabilizes reporter mRNAs targeted for NSD, while a conserved catalytic residue is critical for its function.

Conclusions:

  • Angel1 is a novel human factor essential for the non-stop mRNA decay (NSD) pathway.
  • The catalytic activity of Angel1 plays a critical role in recognizing and processing non-stop mRNAs.
Keywords:
Angel1mRNA turnoverno-go decaynon-stop decayribosome quality control

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