論文 - 詳細
| RRC ID | 83994 |
|---|---|
| 著者 | Meisel JD, Wiesenthal PP, Mootha VK, Ruvkun G. |
| タイトル | CMTR-1 RNA methyltransferase mutations activate widespread expression of a dopaminergic neuron-specific mitochondrial complex I gene. |
| ジャーナル | Curr Biol |
| Abstract |
The mitochondrial proteome is comprised of approximately 1,100 proteins,1 all but 12 of which are encoded by the nuclear genome in C. elegans. The expression of nuclear-encoded mitochondrial proteins varies widely across cell lineages and metabolic states,2,3,4 but the factors that specify these programs are not known. Here, we identify mutations in two nuclear-localized mRNA processing proteins, CMTR1/CMTR-1 and SRRT/ARS2/SRRT-1, which we show act via the same mechanism to rescue the mitochondrial complex I mutant NDUFS2/gas-1(fc21). CMTR-1 is an FtsJ-family RNA methyltransferase that, in mammals, 2'-O-methylates the first nucleotide 3' to the mRNA CAP to promote RNA stability and translation5,6,7,8. The mutations isolated in cmtr-1 are dominant and lie exclusively in the regulatory G-patch domain. SRRT-1 is an RNA binding partner of the nuclear cap-binding complex and determines mRNA transcript fate.9 We show that cmtr-1 and srrt-1 mutations activate embryonic expression of NDUFS2/nduf-2.2, a paralog of NDUFS2/gas-1 normally expressed only in dopaminergic neurons, and that nduf-2.2 is necessary for the complex I rescue by the cmtr-1 G-patch mutant. Additionally, we find that loss of the cmtr-1 G-patch domain cause ectopic localization of CMTR-1 protein to processing bodies (P bodies), phase-separated organelles involved in mRNA storage and decay.10 P-body localization of the G-patch mutant CMTR-1 contributes to the rescue of the hyperoxia sensitivity of the NDUFS2/gas-1 mutant. This study suggests that mRNA methylation at P bodies may control nduf-2.2 gene expression, with broader implications for how the mitochondrial proteome is translationally remodeled in the face of tissue-specific metabolic requirements and stress. |
| 巻・号 | 34(12) |
| ページ | 2728-2738.e6 |
| 公開日 | 2024-6-17 |
| DOI | 10.1016/j.cub.2024.04.079 |
| PII | S0960-9822(24)00593-1 |
| PMID | 38810637 |
| PMC | PMC11265314 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Dopaminergic Neurons* / metabolism Electron Transport Complex I* / genetics Electron Transport Complex I* / metabolism Methyltransferases* / genetics Methyltransferases* / metabolism Mitochondria / genetics Mitochondria / metabolism Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism Mutation* NADH Dehydrogenase / genetics NADH Dehydrogenase / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 23 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tmIs1233 tm4924 tmC24 tm9718 |