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Mapping the MOB proteins proximity network reveals a unique interaction between MOB3C and the RNase P complex

ABSTRACT: Distinct functions mediated by members of the MOB family of proteins remain elusive beyond the evolutionary conserved and well-established roles of MOB1A and B in regulating the Hippo pathway. Since MOB proteins are adaptors, understanding how they engage in protein-protein interactions and complexes assembly is essential to define their biological functions. To address this, we undertook a BioID approach to systematically define the proximity network of the seven mammalian MOB proteins in two different cell lines and we uncovered > 200 interactions, of which at least 70% are unreported on BioGrid. The generated dataset recalled the bona fide interactors of the well-studied MOBs. We further defined the common and differential interactome between different MOBs on a subfamily and an individual level. We defined a unique interaction between MOB3C and 7 out of 10 protein subunits of the RNase P complex, an endonuclease that catalyzes tRNA 5' maturation. As a proof-of-principle for the robustness of the generated dataset, we validated that MOB3C specifically interacts with catalytically active RNase P via affinity purification-mass spectrometry, and pulldowns coupled with pre-tRNA cleavage assay. In summary, our dataset provides novel insights into the biology of MOB proteins and reveals the first interactors of MOB3C, that unexpectedly do not hone in on kinase signaling as for classical MOB1 but rather on an RNA biology territory.

INSTRUMENT(S): Orbitrap Fusion, Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Jean-Francois Cote

PROVIDER: MSV000092406 | MassIVE | Tue Jul 11 23:22:00 BST 2023

REPOSITORIES: MassIVE

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