Heterogeneous nuclear ribonucleoprotein M (HNRNPM)

Heterogeneous nuclear ribonucleoprotein M (HNRNPM) is a ubiquitously expressed nuclear protein belonging to the hnRNP family, possessing three RNA recognition motifs, and functioning in the spliceosome complex to regulate pre-mRNA splicing, mRNA metabolism, and transport. It ensures accurate and precise splicing by blocking cryptic splice sites, thus protecting protein production integrity, and plays critical roles in cell identity, development, and disease. HNRNPM influences cancer metastasis by modulating alternative splicing (notably CD44), and is implicated in muscle differentiation via mTOR signaling, as well as immune responses through cytokine induction and modulation of antiviral functions. The protein can act as a receptor (e.g., for carcinoembryonic antigen in Kupffer cells or N-acetylglucosamine-specific ligands), further expanding its biological scope. Loss or dysfunction of HNRNPM leads to splicing errors, tumor immune activation, and altered cellular responses to stress and pathogens, making it a promising yet complex therapeutic target[3][5][2][1][4][6].

Other names

hnRNP MHNRPMCEAR (carcinoembryonic antigen receptor)NAGR1 (N-acetylglucosamine receptor 1)HNRNPM4HTGR1heterogenous nuclear ribonucleoprotein M4hnRNA-binding protein M4

For putative drugs, the mechanism of action involves modulation or inhibition of splicing activity, especially the usage of cryptic splice sites. This includes targeting alternative splicing events critical for oncogenesis and cellular identity, such as CD44 in breast cancer or SMN2 in spinal muscular atrophy. Additionally, immunomodulation via interferon signaling when hnRNPM is lost is another potential mechanism.