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

Distinct functions mediated by members of the monopolar spindle-one-binder (MOB) family of proteins remain elusive beyond the evolutionarily conserved and well-established roles of MOB1 (MOB1A/B) in regulating tissue homeostasis within the Hippo pathway. Since MOB proteins are adaptors, understanding how they engage in protein-protein interactions, and help assemble complexes is essential to define the full scope of their biological functions. To address this, we undertook a proximity-dependent biotin identification (BioID) approach to define the interactomes of all seven human MOB proteins in HeLa and HEK293 cell lines. We uncovered > 200 interactions, of which at least 70% are unreported on BioGrid. The generated dataset reliably 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 discovered a unique association 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 the specific interaction of MOB3C with catalytically active RNase P by using affinity purification-mass spectrometry and pre-tRNA cleavage assays of MOB3C pulldowns. In summary, our data provide novel insights into the biology of MOB proteins and reveal the first interactors of MOB3C, components of the RNase P complex, and hence an exciting nexus with RNA biology.

Date de publication
1er août 2023
Elkholi IE, Boulais J, Thibault MP, Phan HD, Robert A, Lai LB, Faubert D, Smith M, Gopalan V, Côté JF
Référence PubMed
J Biol Chem 2023:105123
ID PubMed
Montreal Clinical Research Institute (IRCM), Montreal, QC, Canada; Molecular Biology Programs, Université de Montréal, Montreal, QC, Canada; Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada. Electronic address: