HNRNPs

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a family of RNA-binding proteins that associate with nascent transcripts in the nucleus to form ribonucleoprotein particles. They participate in the processing of pre-mRNA and in various aspects of RNA metabolism, including splicing, export, localization, stability, and translation. Many hnRNPs shuttle between the nucleus and cytoplasm and can relocalize in response to cellular signals or stress.

The hnRNP family is large and evolutionarily conserved. Members are encoded by genes such as HNRNPA1, HNRNPA2B1, HNRNPD, HNRNPK, HNRNPL, HNRNPU, and others. They share modular RNA-binding domains—most commonly RNA recognition motifs (RRMs)—and often glycine-rich, arginine-glycine-rich low-complexity regions that mediate protein interactions and phase separation. Expression patterns are often tissue- and developmentally regulated, and individual hnRNPs can have distinct RNA targets.

Functionally, hnRNPs bind to pre-mRNA and mature mRNA to regulate splice site choice and alternative splicing, polyadenylation, mRNA stability, export from the nucleus, localization, and translation. They can act as ligands or antagonists of core splicing factors and influence the assembly of spliceosomal components. Some hnRNPs also participate in ribonucleoprotein particle formation and in stress responses, including the formation of stress granules.

Regulation of hnRNP activity occurs through post-translational modifications such as phosphorylation, methylation, and acetylation, as well as through interactions with other RNA-binding proteins, including SR proteins and components of the spliceosome.

Dysregulation or mutation of hnRNPs has been linked to human disease, notably cancer and neurodegenerative disorders. Mislocalization of hnRNPs in neurons is associated with ALS and related conditions, and altered splicing programs driven by hnRNPs are observed in tumors.