SRSF2 Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SRSF2 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>SRSF2</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Serine and Arginine Rich Splicing Factor 2</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>17q24.3</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein-coding</td>
</tr>
<tr>
<td class="label">Protein Size</td>
<td>30 kDa</td>
</tr>
<tr>
<td class="label">Primary Function</td>
<td>RNA splicing regulation</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/6427" target="_blank">Gene ID: 6427</a></td>
</tr>
</table>
Overview
SRSF2 (Serine and Arginine Rich Splicing Factor 2), also known as SC35, is a member of the SR (serine/arginine-rich) protein family that plays a critical role in RNA metabolism and gene expression regulation. This ~30 kDa phosphoprotein is encoded on chromosome 17q24.3 and functions as a constitutive splicing factor essential for pre-mRNA splicing, mRNA export, and RNA stability. As a component of the spliceosome—the massive ribonucleoprotein complex that catalyzes the removal of introns from pre-mRNA—SRSF2 contributes to the fundamental process of converting primary transcripts into mature messenger RNAs. Beyond its classical splicing functions, SRSF2 participates in diverse post-transcriptional processes critical for maintaining cellular homeostasis and neuronal function.
Function/Biology
SRSF2 exhibits a modular protein architecture consisting of two critical functional domains: an N-terminal RNA Recognition Motif (RRM) responsible for binding to specific RNA sequences, particularly those rich in purine residues, and a C-terminal RS domain (arginine-serine dipeptide repeats) that mediates protein-protein interactions with other spliceosomal components and regulatory proteins. The protein functions in several interconnected biological processes:
RNA Splicing: SRSF2 promotes the recognition of weak splice sites and facilitates interactions between the spliceosome and pre-mRNA substrates, thereby regulating alternative splicing patterns that generate proteomic diversity from limited genomic information.
mRNA Export: Following splicing, SRSF2 remains associated with processed mRNAs as part of the exon junction complex (EJC), promoting their transport from nucleus to cytoplasm through interactions with nuclear export machinery.
Translation Regulation: SRSF2 associated with the EJC influences translation efficiency and accuracy through interactions with translational machinery at ribosome binding sites.
RNA Stability: The protein regulates mRNA degradation pathways, affecting the half-lives of specific transcripts through recruitment of decay-promoting or stabilizing factors.
SRSF2 undergoes dynamic phosphorylation by SRPK1 (SR Protein Kinase 1) and CLK kinases, which regulates its subcellular localization, RNA-binding properties, and protein interactions. This post-translational modification is essential for cycling between functionally distinct splicing factor states.
Role in Neurodegeneration
Emerging evidence implicates SRSF2 dysfunction in multiple neurodegenerative conditions, particularly those characterized by RNA dysmetabolism and proteostasis failure. In frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), aberrant splicing of disease-associated genes appears linked to impaired SRSF2 function. The protein shows altered localization and expression in brain tissue from patients with neurodegenerative diseases, suggesting pathological sequestration or degradation.
SRSF2 dysfunction can promote accumulation of disease-causing protein isoforms through altered splicing of genes encoding cytoskeletal proteins, RNA-binding proteins, and mitochondrial factors. In particular, aberrant splicing of TDP-43, FUS, and C9orf72 transcripts—all implicated in ALS and FTD—may reflect compromised SRSF2-mediated splicing control. The loss of SRSF2 expression correlates with inclusion body formation, suggesting connections to pathological protein aggregation cascades.
Molecular Mechanisms
The neuropathogenic mechanisms involving SRSF2 include:
**
Pathway Diagram
The following diagram shows the key molecular relationships involving SRSF2 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)