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The Human CCHC-type Zinc Finger Nucleic Acid-Binding Protein Binds G-Rich Elements in Target mRNA Coding Sequences and Promotes Translation
Please always quote using this URN: urn:nbn:de:bvb:20-opus-171122
- 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-transcriptional, 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 ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify 8,420 CNBP binding sites on 4,178 mRNAs.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-transcriptional, 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 ribonucleoside-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.…
Author: | Daniel Benhalevy, Sanjay K. Gupta, Charles H. Danan, Suman Ghosal, Hong-Wei Sun, Hinke G. Kazemeier, Katrin Paeschke, Markus Hafner, Stefan A. Juranek |
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URN: | urn:nbn:de:bvb:20-opus-171122 |
Document Type: | Journal article |
Faculties: | Fakultät für Chemie und Pharmazie / Lehrstuhl für Biochemie |
Language: | English |
Parent Title (English): | Cell Reports |
Year of Completion: | 2017 |
Volume: | 18 |
Issue: | 12 |
Pagenumber: | 2979–2990 |
Source: | Cell Reports 2017, 18(12):2979–2990. DOI: 10.1016/j.celrep.2017.02.080 |
DOI: | https://doi.org/10.1016/j.celrep.2017.02.080 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28329689 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 572 Biochemie |
Tag: | CLIP-seq; PAR-CLIP; RNA binding protein; posttranscriptional gene regulation; ribosome profiling; translational regulation; zinc-finger |
Release Date: | 2019/10/16 |
Licence (German): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |