論文 - 詳細
| RRC ID | 46623 |
|---|---|
| 著者 | Kim S, Johnson W, Chen C, Sewell AK, Byström AS, Han M. |
| タイトル | Allele-specific suppressors of lin-1(R175Opal) identify functions of MOC-3 and DPH-3 in tRNA modification complexes in Caenorhabditis elegans. |
| ジャーナル | Genetics |
| Abstract |
The elongator (ELP) complex consisting of Elp1-6p has been indicated to play roles in multiple cellular processes. In yeast, the ELP complex has been shown to genetically interact with Uba4p/Urm1p and Kti11-13p for a function in tRNA modification. Through a Caenorhabditis elegans genetic suppressor screen and positional cloning, we discovered that loss-of-function mutations of moc-3 and dph-3, orthologs of the yeast UBA4 and KTI11, respectively, effectively suppress the Multivulva (Muv) phenotype of the lin-1(e1275, R175Opal) mutation. These mutations do not suppress the Muv phenotype caused by other lin-1 alleles or by gain-of-function alleles of ras or raf that act upstream of lin-1. The suppression can also be reverted by RNA interference of lin-1. Furthermore, we showed that dph-3(lf) also suppressed the defect of lin-1(e1275) in promoting the expression of a downstream target (egl-17). These results indicate that suppression by the moc-3 and dph-3 mutations is due to the elevated activity of lin-1(e1275) itself rather than the altered activity of a factor downstream of lin-1. We further showed that loss-of-function mutations of urm-1 and elpc-1-4, the worm counterparts of URM1 and ELP complex components in yeast, also suppressed lin-1(e1275). We also confirmed that moc-3(lf) and dph-3(lf) have defects in tRNA modifications as do the mutants of their yeast orthologs. These results, together with the observation of a likely readthrough product from a lin-1(e1275)::gfp fusion transgene indicate that the aberrant tRNA modification led to failed recognition of a premature stop codon in lin-1(e1275). Our genetic data suggest that the functional interaction of moc-3/urm-1 and dph-3 with the ELP complex is an evolutionarily conserved mechanism involved in tRNA functions that are important for accurate translation. |
| 巻・号 | 185(4) |
| ページ | 1235-47 |
| 公開日 | 2010-8-1 |
| DOI | 10.1534/genetics.110.118406 |
| PII | genetics.110.118406 |
| PMID | 20479142 |
| PMC | PMC2927752 |
| MeSH | Amino Acid Sequence Animals Animals, Genetically Modified Blotting, Western Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Gene Expression Regulation, Developmental Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Larva / genetics Larva / growth & development Molecular Sequence Data Mutation Phenotype RNA Interference RNA, Transfer / genetics* RNA, Transfer / metabolism Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Amino Acid Temperature Transcription Factors / genetics* Transcription Factors / metabolism |
| IF | 4.015 |
| 引用数 | 5 |
| WOS 分野 | GENETICS & HEREDITY |
| 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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| 各媒体での言及数の合計 | 0 |
| 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 | tm3742 |