1. Chromosomes and Gene Expression
  2. Genetics and Genomics

Dcp2 C-terminal cis-binding elements control selective targeting of the decapping enzyme by forming distinct decapping complexes

  1. Feng He  Is a corresponding author
  2. Chan Wu
  3. Allan Jacobson  Is a corresponding author
  1. University of Massachusetts Medical School, United States
  2. University of Massachusetts Chan Medical School, United States
https://doi.org/10.7554/eLife.74410
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  1. Feng He
  2. Chan Wu
  3. Allan Jacobson
(2022)
Dcp2 C-terminal cis-binding elements control selective targeting of the decapping enzyme by forming distinct decapping complexes
eLife 11:e74410.
https://doi.org/10.7554/eLife.74410
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Abstract

A single Dcp1-Dcp2 decapping enzyme targets diverse classes of yeast mRNAs for decapping-dependent 5' to 3' decay, but the molecular mechanisms controlling mRNA selectivity by the enzyme remain elusive. Through extensive genetic analyses we reveal that Dcp2 C-terminal domain cis-regulatory elements control decapping enzyme target specificity by orchestrating formation of distinct decapping complexes. Two Upf1-binding motifs direct the decapping enzyme to NMD substrates, a single Edc3-binding motif targets both Edc3 and Dhh1 substrates, and Pat1-binding leucine-rich motifs target Edc3 and Dhh1 substrates under selective conditions. Although it functions as a unique targeting component of specific complexes, Edc3 is a common component of multiple complexes. Scd6 and Xrn1 also have specific binding sites on Dcp2, allowing them to be directly recruited to decapping complexes. Collectively, our results demonstrate that Upf1, Edc3, Scd6, and Pat1 function as regulatory subunits of the holo-decapping enzyme, controlling both its substrate specificity and enzymatic activation.

Data availability

Source data associated with figures of northern blotting analyses have been deposited in the Dryad repository (https://datadryad.org/stash) and within that site can be found at doi:10.5061/dryad.pc866t1px. The availability of source data files is indicated in the text.

The following data sets were generated

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Author details

  1. Feng He

    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    feng.he@umassmed.edu
    Competing interests
    No competing interests declared.

  2. Chan Wu

    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.

  3. Allan Jacobson

    Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, United States
    For correspondence
    allan.jacobson@umassmed.edu
    Competing interests
    Allan Jacobson, is co-founder, director, and Scientific Advisory Board chair for PTC Therapeutics Inc..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5661-3821

Funding

National Institute of General Medical Sciences (MIRA 1R35GM122468)

  • Allan Jacobson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, He et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Feng He
  2. Chan Wu
  3. Allan Jacobson
(2022)
Dcp2 C-terminal cis-binding elements control selective targeting of the decapping enzyme by forming distinct decapping complexes
eLife 11:e74410.
https://doi.org/10.7554/eLife.74410

Share this article

https://doi.org/10.7554/eLife.74410

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