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CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling
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-i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s).
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574844/ https://www.ncbi.nlm.nih.gov/pubmed/33086056 http://dx.doi.org/10.1016/j.celrep.2020.108269 |
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author | Lee, Yen-Lurk Kung, Fan-Che Lin, Chia-Hsuan Huang, Yi-Shuian |
author_facet | Lee, Yen-Lurk Kung, Fan-Che Lin, Chia-Hsuan Huang, Yi-Shuian |
author_sort | Lee, Yen-Lurk |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7574844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Author(s). |
record_format | MEDLINE/PubMed |
spelling | pubmed-75748442020-10-21 CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling Lee, Yen-Lurk Kung, Fan-Che Lin, Chia-Hsuan Huang, Yi-Shuian Cell Rep Report 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. The Author(s). 2020-10-20 2020-10-20 /pmc/articles/PMC7574844/ /pubmed/33086056 http://dx.doi.org/10.1016/j.celrep.2020.108269 Text en © 2020 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Report Lee, Yen-Lurk Kung, Fan-Che Lin, Chia-Hsuan Huang, Yi-Shuian CMTR1-Catalyzed 2′-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2α Expression Independent of RIG-I Signaling |
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 | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574844/ https://www.ncbi.nlm.nih.gov/pubmed/33086056 http://dx.doi.org/10.1016/j.celrep.2020.108269 |
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