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Dcp2 C-terminal Cis-Binding Elements Control Selective Targeting of the Decapping Enzyme by Forming Distinct Decapping Complexes

Feng He, Chan Wu, View ORCID ProfileAllan Jacobson
doi: https://doi.org/10.1101/2021.10.01.462794
Feng He
1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01655
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  • For correspondence: feng.he@umassmed.edu allan.jacobson@umassmed.edu
Chan Wu
1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01655
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Allan Jacobson
1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01655
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  • ORCID record for Allan Jacobson
  • For correspondence: feng.he@umassmed.edu allan.jacobson@umassmed.edu
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SUMMARY

A single Dcp1-Dcp2 decapping enzyme targets diverse classes of yeast mRNAs for decapping-dependent 5’ to 3’ decay, but the molecular mechanisms controlling selective mRNA targeting by the enzyme remain elusive. Through extensive genetic analyses we uncover cis-regulatory elements in the Dcp2 C-terminal domain that control selective targeting of the decapping enzyme by forming distinct decapping complexes. Two Upf1-binding motifs target the decapping enzyme to NMD substrates, and a single Edc3-binding motif targets both Edc3 and Dhh1 substrates. 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. Xrn1 also has a specific Dcp2 binding site, allowing it to be directly recruited to decapping complexes. Collectively, our results demonstrate that Upf1, Edc3, and Pat1 function as regulatory subunits of the holo-decapping enzyme, controlling both its targeting specificity and enzymatic activation.

Highlights Loss of Dcp2 cis-binding elements causes selective stabilization of distinct decapping substrates

Dcp2 cis-binding elements promote the assembly of target-specific decapping complexes in vivo

Xrn1 binds to Dcp2, and both Edc3 and Xrn1 are common components of multiple decapping complexes

Upf1, Edc3, and Pat1 function as unique targeting subunits of the yeast holo-decapping enzyme

Competing Interest Statement

A.J. is co-founder, director, and SAB chair of PTC Therapeutics Inc. All other authors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 01, 2021.
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Dcp2 C-terminal Cis-Binding Elements Control Selective Targeting of the Decapping Enzyme by Forming Distinct Decapping Complexes
Feng He, Chan Wu, Allan Jacobson
bioRxiv 2021.10.01.462794; doi: https://doi.org/10.1101/2021.10.01.462794
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Dcp2 C-terminal Cis-Binding Elements Control Selective Targeting of the Decapping Enzyme by Forming Distinct Decapping Complexes
Feng He, Chan Wu, Allan Jacobson
bioRxiv 2021.10.01.462794; doi: https://doi.org/10.1101/2021.10.01.462794

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