Impaired spliceosomal UsnRNP assembly leads to Sm mRNA down-regulation and Sm protein degradation.

Archana Bairavasundaram Prusty, Rajyalakshmi Meduri, Bhupesh Kumar Prusty, Jens Vanselow, Andreas Schlosser, Utz Fischer

The Journal of cell biology 2017 Aug 07

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Specialized assembly factors facilitate the formation of many macromolecular complexes in vivo. The formation of Sm core structures of spliceosomal U-rich small nuclear ribonucleoprotein particles (UsnRNPs) requires assembly factors united in protein arginine methyltransferase 5 (PRMT5) and survival motor neuron (SMN) complexes. We demonstrate that perturbations of this assembly machinery trigger complex cellular responses that prevent aggregation of unassembled Sm proteins. Inactivation of the SMN complex results in the initial tailback of Sm proteins on the PRMT5 complex, followed by down-regulation of their encoding mRNAs. In contrast, reduction of pICln, a PRMT5 complex subunit, leads to the retention of newly synthesized Sm proteins on ribosomes and their subsequent lysosomal degradation. Overexpression of Sm proteins under these conditions results in a surplus of Sm proteins over pICln, promoting their aggregation. Our studies identify an elaborate safeguarding system that prevents individual Sm proteins from aggregating, contributing to cellular UsnRNP homeostasis. © 2017 Prusty et al.

Citation

Archana Bairavasundaram Prusty, Rajyalakshmi Meduri, Bhupesh Kumar Prusty, Jens Vanselow, Andreas Schlosser, Utz Fischer. Impaired spliceosomal UsnRNP assembly leads to Sm mRNA down-regulation and Sm protein degradation. The Journal of cell biology. 2017 Aug 07;216(8):2391-2407