Non-redundant roles for the human mRNA decapping cofactor paralogs DCP1a and DCP1b.
Publication/Presentation Date
11-1-2024
Abstract
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.
Volume
7
Issue
11
ISSN
2575-1077
Published In/Presented At
Vukovic, I., Barnada, S. M., Ruffin, J. W., Karlin, J., Lokareddy, R. K., Cingolani, G., & McMahon, S. B. (2024). Non-redundant roles for the human mRNA decapping cofactor paralogs DCP1a and DCP1b. Life science alliance, 7(11), e202402938. https://doi.org/10.26508/lsa.202402938
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
39256052
Department(s)
Administration and Leadership
Document Type
Article