CLIP-seq analysis of cytoplasmic poly(A) binding protein-1 reveals binding to genomically encoded sequences within mammalian mRNAs

Pabpc1 is the major cytoplasmic poly(A) binding protein in mammalian cells. Pabpc1 functions have been characterized predominantly in context of its binding to 3’ poly(A) tails of mRNAs. Here we performed CLIP-seq to identify additional Pabpc1 binding sites within mammalian mRNAs that may impact on gene regulation. Our analysis revealed that Pabpc1 binds directly to the canonical polyadenylation signal on thousands of mRNAs in the mouse transcriptome. Pabpc1 binding was also observed at sites coincident with the translational initiation and termination sites bracketing open reading frames, exemplified by non-polyadenylated replication-dependent histone mRNAs. A less abundant set of Pabpc1 interactions were mapped to A-rich sites within 5’ UTRs in a restricted subset of mRNAs including Pabpc1 itself. Mechanistic analyses of the subset of 5’UTR-Pabpc1 interactions revealed evidence for auto-regulatory and trans-regulatory translational control mediated by defined A/U-rich elements. These data, in their entirety, demonstrate that the repertoire of Pabpc1 binding and actions is substantially broader than previously recognized and has the potential to impact and coordinate post-transcriptional controls over a critical to an array of cellular functions Pabpc1 CLIP-seq (3 replicates) mRNA-seq (2 replicates)