FUS controls the processing of snoRNAs into smaller RNA fragments that can regulate gene expression

FUS is a multifunctional protein involved in many pathways of RNA metabolism in human cells, including transcription, splicing, miRNA processing and replication-dependent histone gene expression. In this paper, we show for the first time that in human cells FUS can mediate the biogenesis of sdRNA, snoRNA-derived RNAs, that can be further involved in the regulation of gene expression. Using RNA immunoprecipitation followed by high throughput sequencing we identified snoRNAs in FUS-immunoprecipitated fraction. The interaction of FUS with a snoRNA fragment was further confirmed by EMSA and double filter binding assay. We observed that FUS negatively influences the level of selected mature snoRNAs in cells. Scanning of available human small RNAs databases revealed the existence of sdRNAs with the length of 19-33 nucleotides, that can be derived from FUS-dependent snoRNAs. Further in silico approach enabled us to predict putative targets for these sdRNAs. Our preliminary results indicate that sdRNAs may bind to the untranslated region of target mRNAs and influence their posttranscriptional stability or translation. Moreover, we identified a sdRNA that can interact with noncoding transcript and destabilize it, which in turn, might stabilize the level of mRNA transcribed from the same genomic region.