The Human CCHC-type Zinc Finger Nucleic Acid-Binding Protein Binds G-Rich Elements in Target mRNA Coding Sequences and Promotes Translation

Daniel Benhalevy, Sanjay K. Gupta, Charles H. Danan, Suman Ghosal, Hong-Wei Sun, Hinke G. Kazemier, Katrin Paeschke, Markus Hafner, Stefan A. Juranek

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    Abstract

    The CCHC-type zinc finger nucleic acid-binding protein (CNBP/ZNF9) is conserved in eukaryotes and is essential for embryonic development in mammals. It has been implicated in transcriptional, as well as post-transcri ptional, gene regulation; however, its nucleic acid ligands and molecular function remain elusive. Here, we use multiple systems-wide approaches to identify CNBP targets and function. We used photoactivatable ribonucleo side-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify 8,420 CNBP binding sites on 4,178 mRNAs. CNBP preferentially bound G-rich elements in the target mRNA coding sequences, most of which were previously found to form G-quadruplex and other stable structures in vitro. Functional analyses, including RNA sequencing, ribosome profiling, and quantitative mass spectrometry, revealed that CNBP binding did not influence target mRNA abundance but rather increased their translational efficiency. Considering that CNBP binding prevented G-quadruplex structure formation in vitro, we hypothesize that CNBP is supporting translation by resolving stable structures on mRNAs.

    Original languageEnglish
    Pages (from-to)2979-2990
    Number of pages12
    JournalCell reports
    Volume18
    Issue number12
    DOIs
    Publication statusPublished - 21-Mar-2017

    Keywords

    • G-QUADRUPLEX STRUCTURES
    • PAR-CLIP
    • GENOME-WIDE
    • C-MYC
    • NUCLEOTIDE RESOLUTION
    • ARGININE METHYLATION
    • MASS-SPECTROMETRY
    • CROSS-LINKING
    • IN-VIVO
    • IDENTIFICATION

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