TARDBP is a human gene. Variants in TARDBP have been implicated in Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), Cancer. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Gene Symbol: SNRPA1
Also Known As: U2A', U2-snRNP-specific protein A
Gene ID (NCBI): 6627
Chromosomal Location: 15q26.3
SNRPA1 (Small Nuclear Ribonucleoprotein Polypeptide A1) is a component of the U2 small nuclear ribonucleoprotein (snRNP) involved in pre-mRNA splicing. It is also known as U2A' and plays a critical role in the assembly and function of the U2 snRNP, which is essential for the spliceosome's recognition of the branch point site during splicing [1][2]. Mutations in splicing factors including SNRPA1 have been implicated in neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) [3].
¶ Protein Structure and Function
SNRPA1 is a 255-amino acid protein that:
- Binds to U2 snRNA as part of the U2 snRNP complex
- Interacts with U2AF (U2 small nuclear RNA auxiliary factor)
- Plays a structural role in stabilizing the U2 snRNP on the pre-mRNA
The spliceosome undergoes complex assembly:
- E complex: U1 snRNP binds 5' splice site
- A complex: U2 snRNP (including SNRPA1) binds branch point site
- B complex: U4/U6.U5 tri-snRNP joins
- C complex: Catalytic steps occur
SNRPA1 stabilizes U2 snRNP binding through protein-protein interactions.
SNRPA1 is expressed in:
- Brain: Throughout cortex, hippocampus, cerebellum, brainstem
- Peripheral tissues: Ubiquitous, high in proliferating cells
- Cell types: Neurons, glial cells, all cell types
Splicing dysregulation is a hallmark of ALS:
- Mutations in splicing factors (TDP-43, FUS,hnRNPA1) cause familial ALS
- SNRPA1 expression altered in sporadic ALS
- Aberrant splicing of survival motor neuron (SMN) transcripts
- TDP-43 pathology affects splicing regulation
- Similar splicing defects as ALS (ALS-FTD spectrum)
- SNRPA1 overexpression in various cancers
- Alternative splicing in tumor cells
- Splice-switching oligonucleotides (SSOs): Correct aberrant splicing
- Small molecule splicing modulators: E7104, H3B-8800
- ** antisense therapy:** Target disease-causing splice variants
- Understanding splicing dysregulation in neurodegeneration
- Developing splicing-correcting therapies
- Biomarker development from splicing patterns
- TARDBP - TDP-43, ALS gene
- FUS - Fused in sarcoma, ALS gene
- HNRNPA1 - hnRNP A1, ALS gene
- SNRPA - SNRPA, related splicing factor
- SRRM2 - Serine/arginine repetitive matrix 2