High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies - PubMed (original) (raw)

. 2018 Feb 1;69(3):517-532.e11.

doi: 10.1016/j.molcel.2017.12.020. Epub 2018 Jan 25.

Wade H Dunham 1, Seo Jung Hong 1, James D R Knight 1, Mikhail Bashkurov 1, Ginny I Chen 2, Halil Bagci 3, Bhavisha Rathod 1, Graham MacLeod 4, Simon W M Eng 5, Stéphane Angers 6, Quaid Morris 7, Marc Fabian 8, Jean-François Côté 9, Anne-Claude Gingras 10

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High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies

Ji-Young Youn et al. Mol Cell. 2018.

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Abstract

mRNA processing, transport, translation, and ultimately degradation involve a series of dedicated protein complexes that often assemble into large membraneless structures such as stress granules (SGs) and processing bodies (PBs). Here, systematic in vivo proximity-dependent biotinylation (BioID) analysis of 119 human proteins associated with different aspects of mRNA biology uncovers 7424 unique proximity interactions with 1,792 proteins. Classical bait-prey analysis reveals connections of hundreds of proteins to distinct mRNA-associated processes or complexes, including the splicing and transcriptional elongation machineries (protein phosphatase 4) and the CCR4-NOT deadenylase complex (CEP85, RNF219, and KIAA0355). Analysis of correlated patterns between endogenous preys uncovers the spatial organization of RNA regulatory structures and enables the definition of 144 core components of SGs and PBs. We report preexisting contacts between most core SG proteins under normal growth conditions and demonstrate that several core SG proteins (UBAP2L, CSDE1, and PRRC2C) are critical for the formation of microscopically visible SGs.

Keywords: BioID; PP4 complex; PRRC2C; UBAP2L; mass spectrometry; membraneless organelle; processing body; proximity-based labeling; ribonucleoprotein complex; stress granule.

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