Regulation of Cellular RNA Nano-Particle Assembly by Splicing Factor SRp20

Abstract

Cellular RNA nano-particles (RNA granules) such as stress granule (SG) and P-body (PB) are translationally silenced mRNA-protein complexes. Previously, a genome-wide loss-of-function screen using oligomeric siRNAs targeting potential drug target genes was performed to identify genes that are involved in SG and PB assembly. SRp20 (SRSF3), a splicing regulator, was identified as a potential regulator for the RNA granule assembly. Here, we show that SRp20 is a bona-fide RNA granule component using antibody against SRp20 as well as Flag-tagged SRp20 through immunofluorescence microscopy. More importantly, upon knockdown of SRp20 using siRNA, RNA granule formation was potently disrupted indicating that SRp20 is one of the major structural components of SGs and PBs. Interestingly, polysome profiling analyses displayed that SRp20 is distributed in all ribosomal fractions suggesting a potential role of SRp20 as a post-transcriptional mRNA regulator. These results broaden the functional role of SRp20 from the nuclear RNA processing events to the cytoplasmic post-transcriptional mRNA regulatory events through RNA granules that are critical for the regulation of gene expression.