Non-redundant roles for the human mRNA decapping cofactor paralogs DCP1a and DCP1b.

Autor:	Vukovic I; https://ror.org/00ysqcn41 Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA., Barnada SM; https://ror.org/00ysqcn41 Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA., Ruffin JW, Karlin J; https://ror.org/00ysqcn41 Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA., Lokareddy RK; https://ror.org/008s83205 Academic Joint Departments - Biochemistry & Molecular Genetic, University of Alabama at Birmingham, Birmingham, AL, USA., Cingolani G; https://ror.org/008s83205 Academic Joint Departments - Biochemistry & Molecular Genetic, University of Alabama at Birmingham, Birmingham, AL, USA., McMahon SB; https://ror.org/00ysqcn41 Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA Steven.McMahon@jefferson.edu.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2024 Sep 10; Vol. 7 (11). Date of Electronic Publication: 2024 Sep 10 (Print Publication: 2024).
DOI:	10.26508/lsa.202402938
Abstrakt:	Eukaryotic gene expression is regulated at the transcriptional and post-transcriptional levels, with disruption of regulation contributing significantly to human diseases. The 5' m7G mRNA cap is a central node in post-transcriptional regulation, participating in both mRNA stabilization and translation efficiency. In mammals, DCP1a and DCP1b are paralogous cofactor proteins of the mRNA cap hydrolase DCP2. As lower eukaryotes have a single DCP1 cofactor, the functional advantages gained by this evolutionary divergence remain unclear. We report the first functional dissection of DCP1a and DCP1b, demonstrating that they are non-redundant cofactors of DCP2 with unique roles in decapping complex integrity and specificity. DCP1a is essential for decapping complex assembly and interactions between the decapping complex and mRNA cap-binding proteins. DCP1b is essential for decapping complex interactions with protein degradation and translational machinery. DCP1a and DCP1b impact the turnover of distinct mRNAs. The observation that different ontological groups of mRNA molecules are regulated by DCP1a and DCP1b, along with their non-redundant roles in decapping complex integrity, provides the first evidence that these paralogs have qualitatively distinct functions. (© 2024 Vukovic et al.)
Databáze:	MEDLINE
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