Comparative analyses of vertebrate CPEB-family of proteins define two sub-families with distinct, but coordinated, functions in post-transcriptional regulation of gene expression

ABSTRACT: Background: The vertebrate CPEB-family of RNA-binding proteins promote translational repression or activation of their target mRNAs, which harbor cytoplasmic polyadenylation elements (CPEs) in their 3’ UTRs, through cytoplasmic changes in their poly(A) tail lengths. However, their regulation(s) and mechanism(s) of action have not been systematically addressed as a family. Results: Here we perform a comparative analysis of the four vertebrate CPEBs in their regulation by phosphorylation, supramolecular assemblies’ composition and properties and in their mRNA targets. Conclusions: We show that although all four CPEBs are able to recruit CCR4-NOT deadenylation complex when not phosphorylated, their mechanisms of action determine two subfamilies with distinct, but coordinated, regulation by phosphorylation and target specificity. Thus, CPEB1 forms ribonucleoprotein complexes that are remodeled upon a single phosphorylation event, by AurkA, and are associated with mRNAs containing canonical CPEs. On the other hand, CPEB2-4 are regulated by multiple proline-directed phosphorylations that control their liquid-liquid phase-separation. CPEB2-4 mRNA-targets include CPEB1-bound transcripts, with canonical CPEs, but also a specific subset of mRNAs with non-canonical CPEs. In turn, CPEB2-4 coacervates display compositional, morphological and dynamic differences. Altogether, these results show how, globally, the CPEB family of proteins is able to integrate cellular cues to generate a finetuned adaptive response in gene expression regulation.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Xenopus Laevis (african Clawed Frog)

TISSUE(S): Oocyte

SUBMITTER: Marina Gay  

LAB HEAD: Raul Mendez

PROVIDER: PXD033349 | Pride | 2022-10-05

REPOSITORIES: Pride