HNRNPU

HNRNPU, also known as heterogeneous nuclear ribonucleoprotein U or scaffold attachment factor A (SAF-A), is a human protein encoded by the HNRNPU gene. It is a member of the heterogeneous nuclear ribonucleoprotein family and resides primarily in the cell nucleus. The protein is involved in binding both RNA and DNA and participates in multiple facets of RNA metabolism and chromatin biology.

HNRNPU is enriched in the nucleus where it associates with scaffold/matrix attachment regions (MARs) of the genome. Through this interaction, the protein contributes to higher-order chromatin organization and the maintenance of nuclear architecture. It is also implicated in RNA processing events, including pre-mRNA splicing and mRNA stability, and can influence transcriptional regulation and RNA export. The protein often functions as part of multiprotein complexes that coordinate gene expression and genome organization.

Biological significance of HNRNPU is broad and it is widely expressed across tissues. In model organisms, the protein has been shown to be essential for normal development, reflecting its roles in chromatin structure and RNA metabolism. Disruption of HNRNPU can perturb gene expression programs and nuclear organization, with consequences for cell function.

Clinical relevance is highlighted by the association of HNRNPU variants with human disease. De novo loss-of-function mutations and haploinsufficiency in HNRNPU have been linked to neurodevelopmental disorders, including intellectual disability and epileptic encephalopathy, often accompanied by developmental delays and seizures. The spectrum and penetrance of symptoms can vary among affected individuals.

In research, HNRNPU is studied for its contributions to RNA processing, chromatin dynamics, and responses to cellular stress, reflecting its central role in coordinating nuclear activities that influence gene expression.