CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling
Summary: Eukaryotic mRNAs are 5′ end capped with a 7-methylguanosine, which is important for processing and translation of mRNAs. Cap methyltransferase 1 (CMTR1) catalyzes 2′-O-ribose methylation of the first transcribed nucleotide (N1 2′-O-Me) to mask mRNAs from innate immune surveillance by retino...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720312584 |
| _version_ | 1819170434706309120 |
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| author | Yen-Lurk Lee Fan-Che Kung Chia-Hsuan Lin Yi-Shuian Huang |
| author_facet | Yen-Lurk Lee Fan-Che Kung Chia-Hsuan Lin Yi-Shuian Huang |
| author_sort | Yen-Lurk Lee |
| collection | DOAJ |
| description | Summary: Eukaryotic mRNAs are 5′ end capped with a 7-methylguanosine, which is important for processing and translation of mRNAs. Cap methyltransferase 1 (CMTR1) catalyzes 2′-O-ribose methylation of the first transcribed nucleotide (N1 2′-O-Me) to mask mRNAs from innate immune surveillance by retinoic-acid-inducible gene-I (RIG-I). Nevertheless, whether this modification regulates gene expression for neuronal functions remains unexplored. Here, we find that knockdown of CMTR1 impairs dendrite development independent of secretory cytokines and RIG-I signaling. Using transcriptomic analyses, we identify altered gene expression related to dendrite morphogenesis instead of RIG-I-activated interferon signaling, such as decreased calcium/calmodulin-dependent protein kinase 2α (Camk2α). In line with these molecular changes, dendritic complexity in CMTR1-insufficient neurons is rescued by ectopic expression of CaMK2α but not by inactivation of RIG-I signaling. We further generate brain-specific CMTR1-knockout mice to validate these findings in vivo. Our study reveals the indispensable role of CMTR1-catalyzed N1 2′-O-Me in gene regulation for brain development. |
| first_indexed | 2024-12-22T19:35:20Z |
| format | Article |
| id | doaj.art-62072538263a4dac914fb3917585f521 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T19:35:20Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-62072538263a4dac914fb3917585f5212022-12-21T18:15:00ZengElsevierCell Reports2211-12472020-10-01333108269CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I SignalingYen-Lurk Lee0Fan-Che Kung1Chia-Hsuan Lin2Yi-Shuian Huang3Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 11529, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Yang-Ming University and Academia Sinica, Taipei 11529, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 11529, Taiwan; Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Yang-Ming University and Academia Sinica, Taipei 11529, Taiwan; Corresponding authorSummary: Eukaryotic mRNAs are 5′ end capped with a 7-methylguanosine, which is important for processing and translation of mRNAs. Cap methyltransferase 1 (CMTR1) catalyzes 2′-O-ribose methylation of the first transcribed nucleotide (N1 2′-O-Me) to mask mRNAs from innate immune surveillance by retinoic-acid-inducible gene-I (RIG-I). Nevertheless, whether this modification regulates gene expression for neuronal functions remains unexplored. Here, we find that knockdown of CMTR1 impairs dendrite development independent of secretory cytokines and RIG-I signaling. Using transcriptomic analyses, we identify altered gene expression related to dendrite morphogenesis instead of RIG-I-activated interferon signaling, such as decreased calcium/calmodulin-dependent protein kinase 2α (Camk2α). In line with these molecular changes, dendritic complexity in CMTR1-insufficient neurons is rescued by ectopic expression of CaMK2α but not by inactivation of RIG-I signaling. We further generate brain-specific CMTR1-knockout mice to validate these findings in vivo. Our study reveals the indispensable role of CMTR1-catalyzed N1 2′-O-Me in gene regulation for brain development.http://www.sciencedirect.com/science/article/pii/S22111247203125842′-O-ribose methylationCaMK2cap1 modificationCMTRdendrite developmentinnate immunity |
| spellingShingle | Yen-Lurk Lee Fan-Che Kung Chia-Hsuan Lin Yi-Shuian Huang CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling Cell Reports 2′-O-ribose methylation CaMK2 cap1 modification CMTR dendrite development innate immunity |
| title | CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling |
| title_full | CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling |
| title_fullStr | CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling |
| title_full_unstemmed | CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling |
| title_short | CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling |
| title_sort | cmtr1 catalyzed 2 o ribose methylation controls neuronal development by regulating camk2α expression independent of rig i signaling |
| topic | 2′-O-ribose methylation CaMK2 cap1 modification CMTR dendrite development innate immunity |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720312584 |
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