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Nonsense-mediated mRNA Decay02:27

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Related Experiment Video

Updated: Mar 16, 2026

Measurement of mRNA Decay Rates in Saccharomyces cerevisiae Using rpb1-1 Strains
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Measurement of mRNA Decay Rates in Saccharomyces cerevisiae Using rpb1-1 Strains

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Dis3l2-Mediated Decay Is a Quality Control Pathway for Noncoding RNAs.

Mehdi Pirouz1, Peng Du1, Marzia Munafò2

  • 1Division of Hematology/Oncology, Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Cell Reports
|August 9, 2016
PubMed
Summary

The exonuclease DIS3L2 degrades uridylated noncoding RNAs, acting as a crucial quality control mechanism. This pathway, Dis3l2-mediated decay (DMD), eliminates aberrant ncRNAs and is vital for preventing diseases like Wilms tumors.

Keywords:
7SLDis3l2RmrpTUTaseZcchc11Zcchc6lncRNAsnRNAuridylation

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Area of Science:

  • Molecular Biology
  • RNA Biology
  • Genetics

Background:

  • Mutations in the exonuclease DIS3L2 are linked to Perlman syndrome and Wilms tumorigenesis.
  • DIS3L2 was previously known to degrade uridylated pre-microRNA, but its broader role was unclear.

Purpose of the Study:

  • To identify DIS3L2 targets using an unbiased approach in mouse embryonic stem cells.
  • To investigate the role of DIS3L2 in the decay of noncoding RNAs (ncRNAs).

Main Methods:

  • RNA immunoprecipitation (RIP) to identify DIS3L2-bound RNAs.
  • Deep sequencing to analyze RNA 3' ends and uridylation.
  • Biochemical assays to confirm the decay pathway.

Main Results:

  • DIS3L2 binds and degrades uridylated long noncoding RNAs (lncRNAs) like Rmrp and 7SL, and small nuclear RNAs (snRNAs).
  • These uridylated ncRNAs accumulate in the cytoplasm when DIS3L2 is depleted.
  • Terminal uridylyl transferases (TUTases) Zcchc6/11 are implicated in the uridylation of these ncRNAs.

Conclusions:

  • DIS3L2-mediated decay (DMD) is a quality-control pathway for eliminating aberrant ncRNAs.
  • This pathway involves the uridylation of ncRNAs by TUTases followed by DIS3L2-dependent degradation.
  • DMD plays a significant role in maintaining RNA homeostasis and preventing disease.