SRSF9 Protein is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
UniProt ID: Q13191
Gene: SRSF9
PDB Structures: 1X4A, 2O3D
Molecular Weight: ~25 kDa
Subcellular Localization: Nucleus (splicing speckles)
Protein Family: SR family of splicing factors
SRSF9 (Serine/Arginine-rich splicing factor 9) contains one N-terminal RNA recognition motif (RRM1) and a C-terminal serine/arginine-rich (RS) domain. The RS domain is extensively phosphorylated by SRPK kinases, which regulates its subcellular localization and splicing activity. The RRM mediates sequence-specific RNA binding to exonic splicing enhancers (ESEs).
SRSF9 is a member of the SR protein family that functions as an essential splicing factor. In the nervous system, SRSF9:
- Regulates alternative splicing of neuronal-specific exons
- Controls inclusion of tau (MAPT) exon 10
- Participates in synaptic protein splicing (NLGN1, NRXN1)
- Modulates mRNA export from nucleus
- Functions in transcription elongation through interactions with RNA pol II
- SRSF9 is sequestered into stress granules in ALS
- Dysregulated SRSF9 splicing activity contributes to TDP-43 pathology
- Altered expression of SRSF9 targets in motor neurons
- Interaction with ALS-linked proteins (FUS, TDP-43)
- Aberrant SRSF9 activity leads to tau exon 10 mis-splicing
- Contributes to 3R/4R tau ratio imbalance
- Altered SR protein phosphorylation in AD brain
- Links to amyloid-beta (Aβ) toxicity via splicing dysregulation
- SRSF9 dysfunction in FTD-TDP pathology
- Aberrant splicing of TDP-43 target pre-mRNAs
- Contributes to neuronal vulnerability
- SRPK inhibitors: SRPKIN-1, SRPKII-1 (in pre-clinical development)
- Modulation of RS domain phosphorylation: Kinase inhibitors targeting SRPK1/2
- Antisense oligonucleotides: ASOs to modulate specific SRSF9 splicing events
- Research compounds: splice-switching oligonucleotides (SSOs)
- SR protein dysregulation in ALS (Nat Neurosci, 2019)
- SRSF9 and tau exon 10 splicing in AD (J Biol Chem, 2018)
- SR proteins in neurodegenerative disease (Trends Neurosci, 2020)
- Stress granule composition in ALS (Cell, 2017)
- Phosphorylation of SR proteins in brain (Mol Cell Neurosci, 2021)