RT Journal Article
SR Electronic
T1 FUS controls the processing of snoRNAs into smaller RNA fragments that can regulate gene expression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 409250
DO 10.1101/409250
A1 Patrycja Plewka
A1 Michal Wojciech Szczesniak
A1 Agata Stepien
A1 Marek Zywicki
A1 Andrzej Pacak
A1 Martino Colombo
A1 Izabela Makalowska
A1 Marc-David Ruepp
A1 Katarzyna Dorota Raczynska
YR 2019
UL http://biorxiv.org/content/early/2019/02/04/409250.abstract
AB FUS is a multifunctional protein involved in many steps of RNA metabolism, including transcription, splicing, miRNA processing and replication-dependent histone gene expression. In this paper, we show for the first time that FUS binds and negatively regulates the levels of a subset of snoRNAs in cells. Scanning of available human small RNA databases revealed the existence of smaller RNA fragments that can be processed from FUS-dependent snoRNAs. Therefore, we suggest that FUS mediates the biogenesis of snoRNA-derived small RNAs, called sdRNAs. Further in silico approaches enabled us to predict putative targets of selected FUS-dependent sdRNAs. Our results indicate that sdRNAs may bind to different regions of target mRNAs as well as to noncoding transcripts and influence the posttranscriptional level or translation of these targets.SIGNIFICANCE STATEMENT RNA metabolism is orchestrated by a complex network of RNA-protein interactions and involves various classes of RNA molecules. Small nucleolar RNAs (snoRNAs) are commonly considered essential components of the ribosome biogenesis pathway. However, recent studies have revealed that snoRNAs can also be fragmented into small entities called snoRNA-derived RNAs (sdRNAs), which have been linked to multiple cancer types and thus may serve as next-generation prognostic or diagnostic biomarkers. In this paper, a multifunctional protein, FUS, was shown to be involved in the biogenesis of snoRNA-derived fragments. Furthermore, we combined bioinformatic analyses with complementary experimental approaches to elucidate the role of FUS-dependent sdRNAs in gene expression regulation. Our findings reveal the considerable regulatory potential of this new class of small noncoding RNAs.