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

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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

1. He F
2. Wu C
3. Jacobson A
(2021) Dcp2 C-terminal cis-binding elements control selective targeting of the decapping enzyme by forming distinct decapping complexes
Dryad Digital Repository, doi:10.5061/dryad.pc866t1px.

https://dx.doi.org/10.5061/dryad.pc866t1px

Article and author information

Author details

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.
Chan Wu

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States

Competing interests
No competing interests declared.
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..

"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

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.