Arribas-Layton M, Dennis J, Bennett EJ, Damgaard CK, Lykke-Andersen J

Processing Bodies (PBs) are conserved cytoplasmic aggregations of translationally repressed mRNAs assembled with mRNA decay factors. The aggregation of mRNA-protein (mRNP) complexes into PBs involves interactions between low complexity regions of protein components of the mRNPs. In Saccharomyes cerevisiae, the carboxy- (C-)terminal Q/N-rich domain of the Lsm4 subunit of the ...

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Lsm1-7 complex plays an important role in PB formation, but the C-terminal domain of Lsm4 in most eukaryotes are RGG domains rather than Q/N-rich. Here we show that the Lsm4 RGG domain promotes PB accumulation in human cells, and that symmetric dimethylation of arginines within the RGG domain stimulates this process. An Lsm4 mutant lacking the RGG domain failed to rescue PB formation in cells depleted of endogenous Lsm4, despite this mutant retaining the ability to assemble with Lsm1-7, associate with decapping factors, and promote mRNA decay and translational repression. Mutation of the symmetrically dimethylated arginines within the RGG domain impaired the ability of Lsm4 to promote PB accumulation. Depletion of PRMT5, the primary protein arginine methyltransferase responsible for symmetric arginine dimethylation, including Lsm4, resulted in loss of PBs. We also uncovered the HAT1-RBBP7 lysine acetylase complex as an interaction partner of the Lsm4 RGG domain, but found no evidence for a role of this complex in PB metabolism. Together our findings suggest a stimulatory role for post-translational modifications in PB accumulation and raise the possibility that mRNP dynamics could be post-translationally regulated.

Date: May. 31, 2016

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