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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.
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CLIP-seq, poly(A) binding protein, polyadenylation signal, and translational control
Kini, H. K., Silverman, I. M., Ji, X., Gregory, B. D., & Liebhaber, S. A. (2016). Cytoplasmic Poly(A) Binding Protein-1 Binds to Genomically Encoded Sequences Within Mammalian mRNAs. RNA, 22 (1), 61-74. http://dx.doi.org/10.1261/rna.053447.115
Additional FilesSupplemental_Data_Cytoplasmic Poly(A) Binding Protein-1.pdf (298 kB)
SuppLegends_Cytoplasmic Poly(A) Binding Protein-1.docx (115 kB)
FigureS1_Cytoplasmic Poly(A) Binding Protein-1.jpg (194 kB)
FigureS2_Cytoplasmic Poly(A) Binding Protein-1.jpg (914 kB)
FigureS3_Cytoplasmic Poly(A) Binding Protein-1.jpg (123 kB)
FigureS4_Cytoplasmic Poly(A) Binding Protein-1.jpg (762 kB)
Supplemental_Table_1_Cytoplasmic Poly(A) Binding Protein-1.xls (1613 kB)
Supplemental_Table_2_Cytoplasmic Poly(A) Binding Protein-1.xls (1478 kB)
Supplemental_Table_3_Cytoplasmic Poly(A) Binding Protein-1.xls (330 kB)
Date Posted:10 July 2017
This document has been peer reviewed.