SRSF1

What is SRSF1 Protein?

SRSF1 gene (serine and arginine rich splicing factor 1) is a protein coding gene which situated on the long arm of chromosome 17 at locus 17q22. SRSF1 protein is a highly conserved splicing factor in eukaryotes and belongs to the SR protein family. It contains one or more serine - and arginine-rich regions that are critical for protein-protein interactions during RNA binding and splicing. SRSF1 is involved in mRNA precursor splicing in the nucleus, promoting the correct selection of splicing sites by recognizing and binding specific RNA sequences, thereby influencing gene expression and protein diversity. The SRSF1 protein is consisted of 248 amino acids and SRSF1 molecular weight is approximately 27.7 kDa.

What is the Function of SRSF1 Protein?

The activity and function of SRSF1 are finely regulated by post-translational modifications such as phosphorylation and ubiquitination, which affect its ability to bind to RNA and its role in the splicing process. SRSF1 is able to recognize specific sequences on pre-mRNA and help assemble the splicing complex, which is crucial for selecting the right splicing site. SRSF1 contributes to the generation of multiple mRNA variants by promoting or inhibiting the use of certain splicing sites, thereby increasing protein diversity. SRSF1 is involved in regulating the expression of cell cycle-related genes and gene expression regulation under cellular stress conditions.

Fig1. The multi-functional SR protein SRSF1. (Shipra Das, 2014)

SRSF1 Related Signaling Pathway

The SRSF1 protein plays a role in a variety of biological processes, including mRNA splicing, mRNA stability regulation, transcriptional elongation, and post-transcriptional translation. It affects gene expression by preventing exon jumping, ensuring the accuracy of splicing, and regulating alternative splicing. SRSF1 also has roles in different biological pathways, such as the cell cycle, ubiquitin mediated proteolysis, nucleotide excisional repair, p53 pathway, apoptosis, DNA replication, and RNA degradation. In addition, SRSF1 is also involved in the post-transcriptional regulation of genes related to sexual development, and in the mouse GT1-7 cell model, SRSF1 is regulated through miR-505, affecting the expression of sex hormone releasing hormone and Kiss1 gene. In the late development and maturation of thymus T cells, SRSF1, as a key post-transcriptional regulator, is crucial for the differentiation, proliferation and survival of thymus cells by directly binding and regulating mRNA expression levels of genes closely related to T cell development.

SRSF1 Related Diseases

The abnormal function of SRSF1 protein is associated with many diseases, especially in the field of cancer, and its abnormal expression or the change of splicing pattern is closely related to the occurrence, development and prognosis of tumors. For example, in many types of cancer, such as prostate, lung, breast, colon, and glioblastoma, SRSF1 may lead to the inactivation of tumor suppressor genes or the activation of oncogenes by affecting the alternative splicing of mRNA. In addition, SRSF1 may also be involved in mRNA translation and chemical resistance or radiosensitivity of cancer, thus playing a role in tumor cell proliferation, migration, invasion and apoptosis.

Bioapplications of SRSF1

Due to its central role in mRNA splicing and its association with a variety of cancers, SRSF1 protein's relevant off-the-shelf applications are mainly concentrated in the field of biomedical research and drug development. Although there are currently no approved drugs that directly target SRSF1, in-depth studies of SRSF1's function could help identify its specific role in disease development, potentially providing targets for the development of new therapeutic strategies, particularly in cancer treatment. In addition, the expression level and activity of SRSF1 can also be used as biomarkers for disease diagnosis and prognosis assessment.

Case Study 1: Hongda Liu, 2021

This study aimed at investigating the upstream modulators and clinical relevance of Mnk2 alternative splicing in colon adenocarcinoma (CAC). PCR, western blotting and immunohistochemistry (IHC) were performed to assess the expression of Mnk2 and upstream proteins in CAC. The function of Mnk2 and its regulators were demonstrated in different CAC cell lines as well as in xenograft models. The results showed that he SRSF1 was further confirmed to be the major splicing factor targeting MKNK2 in CAC cells. Higher expression of SRPK1/2 or decreased activity of PP1α were responsible for enhancing SRSF1 phosphorylation and nucleus translocation, subsequently resulted in a switch of MKNK2 alternative splicing.

Fig1. Protein levels of SRSF1 in clinical specimens were also tested by western blotting.

Fig2. The kinase activity of SRPK1/2 targeting SRSF1 was tested by in vitro kinase assay.

Case Study 2: Yi-Fan Xu, 2020

The aim of this study was to identify RNA binding proteins responsible for selective enrichment of exosome miRNAs in cancer cells. A biotin-labeled miR-1246 probe was used to capture RNA binding proteins (RBPs) from PANC-1 cells. Among the RBPs identified through proteomic analysis, SRSF1, EIF3B and TIA1 were highly associated with the miR-1246 probe. RNA immunoprecipitation (RIP) and electrophoretic mobility shift assay (EMSA) confirmed the binding of SRSF1 to miR-1246. Lentivirus shRNA knockdown of SRSF1 in pancreatic cancer cells selectively reduced exosome miRNA enrichment whereas GFP-SRSF1 overexpression enhanced the enrichment as analyzed by next generation small RNA sequencing and qRT-PCR. miRNA sequence motif analysis identified a common motif shared by 36/45 of SRSF1-associated exosome miRNAs. EMSA confirmed that shared motif decoys inhibit the binding of SRSF1 to the miR-1246 sequence.

Fig3. Representative nanoparticle tracking analysis of exosomes (small EVs) derived from control and SRSF1 knockdown PANC-1 cells.

Fig4. EMSA detection of the SRSF1-miR-1246 complex.

SRSF1 has several biochemical functions, for example, RNA binding,RS domain binding,mRNA binding. Some of the functions are cooperated with other proteins, some of the functions could acted by SRSF1 itself. We selected most functions SRSF1 had, and list some proteins which have the same functions with SRSF1. You can find most of the proteins on our site.

SRSF1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SRSF1 here. Most of them are supplied by our site. Hope this information will be useful for your research of SRSF1.

NXF1;SRPK1;Srpk1;NFYA;RNPS1