Heterogeneous nuclear ribonucleoprotein A1

Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a 372-amino-acid RNA-binding protein encoded by HNRNPA1. It functions in pre-mRNA packaging into hnRNP particles, mRNA export from the nucleus to the cytoplasm, and modulation of alternative splicing. hnRNP A1 regulates splicing of pyruvate kinase PKM to produce the M2 isoform and suppresses translation of apoptosis protease activating factor APAF1 by binding to its IRES (UniProt: P09651).

hnRNP A1 is implicated in several neurodegenerative conditions. Mutations are associated with inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD3), amyotrophic lateral sclerosis 20 (ALS20), and distal myopathy 3 (MPD3) (UniProt: P09651). These disorders feature motor neuron loss, muscle weakness, and pathologic protein aggregates.

In Alzheimer's disease, hnRNP A1 is down-regulated in post-mortem AD brain compared to age-matched controls (mean log2FC: −0.4461; Chaparral AD proteomics). This decrease was observed in human post-mortem tissue via TMT-labeled quantitative proteomics across subcellular fractions, suggesting potential involvement in AD pathophysiology.