HNRNPD

HNRNPD, encoding heterogeneous nuclear ribonucleoprotein D (AUF1), is a member of the hnRNP family of RNA-binding proteins in humans. AUF1 binds AU-rich elements in the 3' untranslated regions of many mRNAs and influences their stability and translation. In normal conditions, AUF1 promotes rapid decay of many cytokine mRNAs, although its effects can be transcript- and context-dependent, with some transcripts being stabilized under certain cellular states.

The HNRNPD gene produces four major protein isoforms through alternative splicing: p37, p40, p42, and p45. These isoforms share two N-terminal RNA recognition motifs but differ in their C-terminal regions, affecting localization, RNA affinity, and interaction with degradation machinery. AUF1 shuttles between the nucleus and cytoplasm and can relocalize to stress granules or processing bodies under cellular stress.

Functionally, AUF1 binds AREs and recruits decay factors or deadenylases to shorten mRNA half-life, thereby regulating gene expression post-transcriptionally. It can also participate in nucleocytoplasmic export and influence translation of target mRNAs.

Biological and clinical relevance: HNRNPD/AUF1 participates in inflammatory responses, development, and cellular stress adaptation. Dysregulation of AUF1 has been linked to cancer progression, viral replication, and autoimmune or inflammatory diseases, making it a subject of ongoing research for potential biomarkers and therapeutic targets. Interacting partners include components of mRNA decay pathways and other ARE-binding proteins.

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