Heterogeneous nuclear ribonucleoprotein C (HNRNPC)

Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an abundantly expressed RNA-binding protein in the nucleus, crucial for pre-mRNA processing and maintenance of transcriptome integrity[1][2][3]. HNRNPC complexes with nascent heterogeneous nuclear RNAs (hnRNAs) and forms tetrameric structures, generally as hnRNP C1/C2, which bind preferentially to uridine-rich sequences, thereby orchestrating higher-order hnRNP particle assembly and modulating alternative splicing by influencing exon recognition[1]. It acts as a genome-wide sentinel, especially precluding the exonization of Alu elements by competing with splicing factors like U2AF65, thus protecting against aberrant transcript formation[1][2]. HNRNPC also interacts with m6A RNA modifications, integrating epitranscriptomic signals into mature RNA processing[1]. It can function as a dominant-negative regulator by binding to Vitamin D response elements (VDREs), interfering with VDR-mediated transcription and leading to vitamin D resistance when overexpressed[2][3]. Dysregulated expression or function of HNRNPC has been implicated in various human diseases, predominantly cancer, inherited rickets, and ART-related developmental abnormalities[2][3][4]. No approved drugs directly target HNRNPC, but its centrality in RNA regulation makes it a potential, though therapeutically challenging, target for future intervention.

Other names

Heterogeneous nuclear ribonucleoproteins C1/C2hnRNP C1/C2HNRPCHNRNPSNRPCC1C2Nuclear ribonucleoprotein particle C1 proteinNuclear ribonucleoprotein particle C2 proteinMRD74

Not directly targeted by drugs; known mechanisms include modulation of pre-mRNA splicing, competing with U2AF65 for RNA binding, and affecting vitamin D receptor (VDR) mediated gene transcription