title: Cytoplasmic poly(A) binding protein-1 binds to genomically encoded sequences within mammalian mRNAs.
abstract: The functions of the major mammalian cytoplasmic poly(A) binding protein, PABPC1, have been characterized predominantly in the context of its binding to the 3' poly(A) tails of mRNAs. These interactions play important roles in post-transcriptional gene regulation by enhancing translation and mRNA stability. Here, we performed transcriptome-wide CLIP-seq analysis to identify additional PABPC1 binding sites within genomically encoded mRNA sequences that may impact on gene regulation. From this analysis, we found that PABPC1 binds directly to the canonical polyadenylation signal in thousands of mRNAs in the mouse transcriptome. PABPC1 binding also maps to translation initiation and termination sites bracketing open reading frames, exemplified most dramatically in replication-dependent histone mRNAs. Additionally, a more restricted subset of PABPC1 interaction sites comprised A-rich sequences within the 5' UTRs of mRNAs, including Pabpc1 mRNA itself. Functional analyses revealed that these PABPC1 interactions in the 5' UTR mediate both auto- and trans-regulatory translational control. In total, these findings reveal a repertoire of PABPC1 binding that is substantially broader than previously recognized with a corresponding potential to impact and coordinate post-transcriptional controls critical to a broad array of cellular functions.
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Kini
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Silverman
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Gregory
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Liebhaber
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000818:Animals; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism*; D008322:Mammals; D051379:Mice; D041681:NIH 3T3 Cells; D011061:Poly A / Q000378:metabolism; D039122:Poly(A)-Binding Protein I / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D039122:Poly(A)-Binding Protein I; D012333:RNA, Messenger; D011061:Poly A
keywords: CLIP-seq; poly(A) binding protein; polyadenylation signal; translational control