The domains of polypyrimidine tract binding protein have distinct RNA structural preferences

Caroline Clerte, Kathleen B. Hall

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

PTB (polypyrimidine tract binding protein) participates in cellular regulatory functions in the nucleus and the cytoplasm. It binds to internal ribosome entry sites to facilitate their use in cap-independent translation. It binds to polypyrimidine tracts in pre-mRNA introns to repress inclusion of exons. It binds to the 3′ untranslated regions of mRNAs to stabilize the message. These RNAs have various structures, yet PTB binds to all of them. Here, RNAs with structured or unstructured polypyrimidine tracts are bound to the full-length PTB1 protein and two protein subdomains, each containing two RNA recognition motifs. Hairpin loops from c-src and GABA A γ2 pre-mRNAs and from the 3′ terminus of hepatitis C virus (HCV) were compared to a single-stranded polypyrimidine tract from GABA A γ2 pre-mRNA. We conclude that PTB1 RNA binding function is modular: the N-terminal RRMs preferentially bind to short (U/C) tracts displayed in loops, while the RRM3-RRM4 complex preferentially binds to longer flexible RNA sequences. Since it can bind to short and long polypyrimidine tracts, structured or single-stranded, PTB takes on the role of a versatile adaptor protein that facilitates formation of RNA-protein regulatory complexes.

Original languageEnglish
Pages (from-to)2063-2074
Number of pages12
JournalBiochemistry
Volume48
Issue number10
DOIs
StatePublished - Mar 17 2009

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