Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs
Summary: RNA polymerase II transcripts receive a protective 5ʹ,5ʹ-triphosphate-linked 7-methylguanosine (m7G) cap, and its removal by decapping enzymes like DCP2 is critical for initiation of RNA decay. Alternative RNA caps can be acquired when transcription initiation uses metabolites like nicotina...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719316316 |
| _version_ | 1818040542278189056 |
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| author | Hao Wu Lingyun Li Kuan-Ming Chen David Homolka Pascal Gos Fabienne Fleury-Olela Andrew A. McCarthy Ramesh S. Pillai |
| author_facet | Hao Wu Lingyun Li Kuan-Ming Chen David Homolka Pascal Gos Fabienne Fleury-Olela Andrew A. McCarthy Ramesh S. Pillai |
| author_sort | Hao Wu |
| collection | DOAJ |
| description | Summary: RNA polymerase II transcripts receive a protective 5ʹ,5ʹ-triphosphate-linked 7-methylguanosine (m7G) cap, and its removal by decapping enzymes like DCP2 is critical for initiation of RNA decay. Alternative RNA caps can be acquired when transcription initiation uses metabolites like nicotinamide adenine dinucleotide (NAD), generating NAD-RNAs. Here, we identify human NUDT12 as a cytosolic NAD-RNA decapping enzyme. NUDT12 is active only as homodimers, with each monomer contributing to creation of the two functional catalytic pockets. We identify an ∼600-kDa dodecamer complex between bleomycin hydrolase (BLMH) and NUDT12, with BLMH being required for localization of NUDT12 to a few discrete cytoplasmic granules that are distinct from P-bodies. Both proteins downregulate gene expression when artificially tethered to a reporter RNA in vivo. Furthermore, loss of Nudt12 results in a significant upregulation of circadian clock transcripts in mouse liver. Overall, our study points to a physiological role for NUDT12 in the cytosolic surveillance of NAD-RNAs. : Wu et al. identify NUDT12 as a decapping enzyme for NAD-capped RNAs and demonstrate a role for the enzyme in regulation of circadian clock transcripts in mice. They reveal the existence of a BLMH-NUDT12 complex that facilitates localization of NUDT12 to distinct cytoplasmic granules. Keywords: human NUDT12, BLMH, NAD-RNA, m7G, RNA decay, deNADding, circadian clock |
| first_indexed | 2024-12-10T08:16:11Z |
| format | Article |
| id | doaj.art-80fcc94dbe644df886fa950c3301f007 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T08:16:11Z |
| publishDate | 2019-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-80fcc94dbe644df886fa950c3301f0072022-12-22T01:56:27ZengElsevierCell Reports2211-12472019-12-01291344224434.e13Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAsHao Wu0Lingyun Li1Kuan-Ming Chen2David Homolka3Pascal Gos4Fabienne Fleury-Olela5Andrew A. McCarthy6Ramesh S. Pillai7Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, SwitzerlandDepartment of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, SwitzerlandDepartment of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, SwitzerlandDepartment of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, SwitzerlandDepartment of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, SwitzerlandDepartment of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, SwitzerlandEuropean Molecular Biology Laboratory, Grenoble Outstation, 71 avenue des Martyrs, 38042 Grenoble, FranceDepartment of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, Switzerland; Corresponding authorSummary: RNA polymerase II transcripts receive a protective 5ʹ,5ʹ-triphosphate-linked 7-methylguanosine (m7G) cap, and its removal by decapping enzymes like DCP2 is critical for initiation of RNA decay. Alternative RNA caps can be acquired when transcription initiation uses metabolites like nicotinamide adenine dinucleotide (NAD), generating NAD-RNAs. Here, we identify human NUDT12 as a cytosolic NAD-RNA decapping enzyme. NUDT12 is active only as homodimers, with each monomer contributing to creation of the two functional catalytic pockets. We identify an ∼600-kDa dodecamer complex between bleomycin hydrolase (BLMH) and NUDT12, with BLMH being required for localization of NUDT12 to a few discrete cytoplasmic granules that are distinct from P-bodies. Both proteins downregulate gene expression when artificially tethered to a reporter RNA in vivo. Furthermore, loss of Nudt12 results in a significant upregulation of circadian clock transcripts in mouse liver. Overall, our study points to a physiological role for NUDT12 in the cytosolic surveillance of NAD-RNAs. : Wu et al. identify NUDT12 as a decapping enzyme for NAD-capped RNAs and demonstrate a role for the enzyme in regulation of circadian clock transcripts in mice. They reveal the existence of a BLMH-NUDT12 complex that facilitates localization of NUDT12 to distinct cytoplasmic granules. Keywords: human NUDT12, BLMH, NAD-RNA, m7G, RNA decay, deNADding, circadian clockhttp://www.sciencedirect.com/science/article/pii/S2211124719316316 |
| spellingShingle | Hao Wu Lingyun Li Kuan-Ming Chen David Homolka Pascal Gos Fabienne Fleury-Olela Andrew A. McCarthy Ramesh S. Pillai Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs Cell Reports |
| title | Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs |
| title_full | Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs |
| title_fullStr | Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs |
| title_full_unstemmed | Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs |
| title_short | Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs |
| title_sort | decapping enzyme nudt12 partners with blmh for cytoplasmic surveillance of nad capped rnas |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719316316 |
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