Splicing factor SRSF1 expands the regulatory logic of microRNA expression

Abstract

Keyword: RNA binding protein, splicing factor, microRNA, Crosslinking immunoprecipitation 2 AbstractThe serine and arginine-rich splicing factor SRSF1 is an evolutionarily conserved, essential pre-mRNA splicing factor. Through a global protein-RNA interaction survey we discovered SRSF1 binding sites 25-50nt upstream from hundreds of pre-miRNAs. Using primary miRNA-10b as a model we demonstrate that SRSF1 directly regulates microRNA biogenesis both in vitro and in vivo. Selective 2' hydroxyl acylation analyzed by primer extension (SHAPE) defined a structured RNA element located upstream of the precursor miRNA-10b stem loop. Our data support a model where SRSF1 promotes initial steps of microRNA biogenesis by relieving the repressive effects of cis-regulatory elements within the leader sequence.

Exploring the multifunctionality of SR proteins

“…SR proteins also interact with non-coding RNAs, such as small nucleolar RNAs (snoRNAs), microRNA (miRNAs) and long non-coding RNAs (lncRNAs) [ 43 , 60 ]. Binding of SRSF1 and SRSF3 promotes miRNA processing by enhancing Drosha-mediated cleavage in a splicing-independent manner [ 8 , 27 , 33 , 39 ]. SRSF1 regulates maturation of miR-7, which targets the 3′UTR of SRSF1 and represses its own translation [ 61 ].…”

“…SRSF1 regulates maturation of miR-7, which targets the 3′UTR of SRSF1 and represses its own translation [ 61 ]. It also influences the conformation of an inhibitory stem loop in the pri-miR-10b, which enables the hairpin selection by the Microprocessor [ 33 ]. SRSF3 binds to a specific pri-miRNA binding motif (CNNC) [ 49 ], and enhances the processing of CNNC-containing pri-miRNAs through Drosha recruitment [ 40 ].…”