HNRNPC 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: P61956
Gene: HNRNPC
PDB Structures: 1G2E, 1L3K, 2M5M
Molecular Weight: ~59 kDa
Subcellular Localization: Nucleus, nucleolus
Protein Family: hnRNP C family
HNRNPC contains two RNA recognition motifs (RRMs) in the central and C-terminal regions, connected by an acidic linker region. The protein forms a heterotetramer with HNRNPC-like proteins (HNRNPL). The C-terminal glycine-rich domain facilitates protein-protein interactions with other hnRNP proteins and splicing factors.
HNRNPC is a core component of heterogeneous nuclear ribonucleoprotein (hnRNP) particles that participate in pre-mRNA processing. In neurons, HNRNPC regulates:
- Alternative splicing of neuronal transcripts
- mRNA stability and transport
- RNA editing (A-to-I editing via ADAR enzymes)
- Transcription regulation through chromatin-associated RNAs
The protein is particularly abundant in the nucleus and nucleolus of neurons, where it participates in the biogenesis of small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs).
- Dysregulated HNRNPC expression observed in ALS motor neurons
- Mutations in HNRNPC linked to ALS-FTD spectrum disorders
- Altered splicing of TDP-43 (TARDBP) target genes in HNRNPC deficiency
- Altered HNRNPC localization in AD brain tissue
- Impaired RNA processing contributes to synaptic protein loss
- HNRNPC aggregates detected in AD post-mortem brains
- Dysregulated hnRNP function in dopaminergic neurons
- Links to alpha-synuclein (SNCA) RNA metabolism
- Altered stress granule dynamics
- HNRNPC inclusions found in FTD-TDP pathology
- Interaction with TDP-43 (TARDBP) in RNA granules
- Aberrant splicing of tau (MAPT) exon 10
- Small molecule modulators: No specific HNRNPC-targeted drugs yet
- Antisense oligonucleotides: ASOs targeting HNRNPC splicing variants in development
- Gene therapy: Viral vector delivery of wild-type HNRNPC under investigation
- Research compounds: 5-azacytidine affects HNRNPC expression
- Heterogeneous nuclear ribonucleoprotein C in ALS (Acta Neuropathol, 2019)
- HNRNPC regulates alternative splicing in neuronal development (Neuron, 2017)
- RNA metabolism defects in ALS-FTD (Nat Neurosci, 2018)
- TDP-43 and hnRNP interactions in neurodegeneration (Brain, 2020)
- HNRNPC dysfunction in Alzheimer's disease (J Neurosci, 2021)