Polypyrimidine tract-binding protein 1 (PTBP1)

Polypyrimidine tract-binding protein 1 (PTBP1) is a modular RNA-binding protein composed of four RNA recognition motifs (RRMs), structurally classified as a heterogeneous nuclear ribonucleoprotein (hnRNP)[7][4][3]. PTBP1 binds preferentially to polypyrimidine tracts in pre-mRNA introns, where it regulates multiple steps of RNA maturation, including alternative splicing, polyadenylation, mRNA localization, stability, and translation (notably internal ribosome entry site, IRES-mediated translation)[6][4][7][1]. In the nucleus, PTBP1 acts primarily as a splicing repressor by binding to polypyrimidine-rich sequences near splice junctions[7][6], but can both repress and activate splicing in a context-dependent manner by modulating exon definition[2]. PTBP1 additionally serves as an RNA chaperone, remodeling secondary RNA structures to control translation initiation and the fate of specific mRNAs[2][1]. Beyond splicing, it modulates microRNA function and acts as a key regulator of neuronal development—suppression of PTBP1 expression by miR-124 promotes neuronal differentiation[2]. In cancer, overexpression of PTBP1 drives aberrant splicing patterns that favor tumor progression, metabolic reprogramming (such as promoting the PKM2 isoform), and chemoresistance; it is thus studied as a biomarker and potential cancer therapeutic target[2]. PTBP1’s dysregulation is also implicated in viral infection (by facilitating cap-independent translation of viral RNA)[1] and potentially in neurodegenerative disease[2]. PTBP1's interaction with cellular proteins, such as the prosurvival protein MCL1, reveals an additional regulatory axis through which its splicing and translational effects may be modulated[4]. No small-molecule drugs directly targeting PTBP1 are currently approved; its broad role in RNA processing presents both opportunities and challenges for safe therapeutic targeting due to its potential widespread effects on gene expression[2][4].

Other names

Polypyrimidine tract-binding protein 1PTBP1PTBhnRNP IHNRNPIHeterogeneous nuclear ribonucleoprotein IPTB2PTB3PTB4pPTB57 kDa RNA-binding protein PPTB-1heterogeneous nuclear ribonucleoprotein polypeptide I

Modulate alternative splicing; Inhibit/enhance translation via RNA structural modulation