SRSF1
Description
The SRSF1 (serine and arginine rich splicing factor 1) is a protein-coding gene located on chromosome 17.
Serine/arginine-rich splicing factor 1 (SRSF1), also known as alternative splicing factor 1 (ASF1), pre-mRNA-splicing factor SF2 (SF2) or ASF1/SF2 is a protein that in humans is encoded by the SRSF1 gene. ASF/SF2 is an essential sequence specific splicing factor involved in pre-mRNA splicing. SRSF1 is the gene that codes for ASF/SF2 and is found on chromosome 17. The resulting splicing factor is a protein of approximately 33 kDa. ASF/SF2 is necessary for all splicing reactions to occur, and influences splice site selection in a concentration-dependent manner, resulting in alternative splicing. In addition to being involved in the splicing process, ASF/SF2 also mediates post-splicing activities, such as mRNA nuclear export and translation.
== Structure == ASF/SF2 is an SR protein, and as such, contains two functional modules: an arginine-serine rich region (RS domain), where the bulk of ASF/SF2 regulation takes place, and two RNA recognition motifs (RRMs), through which ASF/SF2 interacts with RNA and other splicing factors. These modules have different functions within general splicing factor function.
== Splicing == ASF/SF2 is an integral part of numerous components of the splicing process. ASF/SF2 is required for 5’ splice site cleavage and selection, and is capable of discriminating between cryptic and authentic splice sites.
SRSF1 plays a crucial role in ensuring accurate and efficient pre-mRNA splicing. It acts to prevent exon skipping, a process where exons are mistakenly removed from the final mRNA sequence. Additionally, SRSF1 regulates alternative splicing, a process that allows for the production of multiple protein isoforms from a single gene. SRSF1 interacts with other splicing factors through its RS domains to bridge the 5'- and 3'-splice site binding components, U1 snRNP and U2AF, respectively. This interaction helps to facilitate the assembly of the spliceosome, the intricate machinery responsible for splicing. SRSF1 can stimulate the binding of U1 snRNP to the 5'-splice site, further contributing to the accuracy of splicing. SRSF1 recognizes and binds to specific RNA sequences, including the octamer (5'-RGAAGAAC-3') and decamers (AGGACAGAGC/AGGACGAAGC), both of which are purine-rich motifs. It exhibits a preference for the 5'-CGAGGCG-3' motif in vitro. Notably, three copies of the octamer can function as a potent splicing enhancer, termed the ASF/SF2 splicing enhancer (ASE), which can specifically activate ASE-dependent splicing. Certain isoforms of SRSF1, such as ASF-2 and ASF-3, act as splicing repressors, suggesting a complex regulatory mechanism. Beyond its role in splicing, SRSF1 may also function as an export adapter in mRNA nuclear export, facilitated by the TAP/NXF1 pathway.
SRSF1 is also known as ASF, NEDFBA, SF2, SF2p33, SFRS1, SRp30a.
