| First Author | Lee YL | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 3 | Pages | 108269 |
| PubMed ID | 33086056 | Mgi Jnum | J:300305 |
| Mgi Id | MGI:6489042 | Doi | 10.1016/j.celrep.2020.108269 |
| Citation | Lee YL, et al. (2020) CMTR1-Catalyzed 2'-O-Ribose Methylation Controls Neuronal Development by Regulating Camk2alpha Expression Independent of RIG-I Signaling. Cell Rep 33(3):108269 |
| abstractText | 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 2alpha (Camk2alpha). In line with these molecular changes, dendritic complexity in CMTR1-insufficient neurons is rescued by ectopic expression of CaMK2alpha 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. |
