PTBP1

PTBP1, short for polypyrimidine tract-binding protein 1, is an RNA-binding protein encoded by the PTBP1 gene. It contains four RNA recognition motif (RRM) domains and binds polypyrimidine-rich sequences, particularly U-rich tracts near 3' splice sites, to regulate alternative splicing. Through its binding, PTBP1 can repress selected exons and influence splice site choice; in many contexts it promotes exon skipping, while in others it can enhance inclusion depending on positioning and interacting factors. In addition to splicing, PTBP1 participates in other aspects of RNA metabolism, including mRNA stability, localization, and translation, including internal ribosome entry site (IRES)-mediated initiation.

Expression and evolution: PTBP1 is broadly expressed in many tissues. It has two paralogs in humans, PTBP2 (nPTB) and PTBP3 (ROD1). PTBP1 is generally abundant in non-neural tissues, whereas PTBP2 expression increases during neuronal differentiation and can substitute for some PTBP1 functions. The transition from PTBP1 to PTBP2 is a hallmark of neural development. MicroRNA-124 promotes neuronal differentiation partly by downregulating PTBP1, enabling PTBP2 to regulate neuron-specific splicing programs.

Clinical and research relevance: misregulation of PTBP1- and PTBP2-controlled splicing is associated with cancer and neurodevelopmental disorders. PTBP1 is studied as a regulator of splice-switching events and as a potential therapeutic target in diseases driven by aberrant RNA processing.