論文 - 詳細
| RRC ID | 45906 |
|---|---|
| 著者 | Zinovyeva AY, Bouasker S, Simard MJ, Hammell CM, Ambros V. |
| タイトル | Mutations in conserved residues of the C. elegans microRNA Argonaute ALG-1 identify separable functions in ALG-1 miRISC loading and target repression. |
| ジャーナル | PLoS Genet |
| Abstract |
microRNAs function in diverse developmental and physiological processes by regulating target gene expression at the post-transcriptional level. ALG-1 is one of two Caenorhabditis elegans Argonautes (ALG-1 and ALG-2) that together are essential for microRNA biogenesis and function. Here, we report the identification of novel antimorphic (anti) alleles of ALG-1 as suppressors of lin-28(lf) precocious developmental phenotypes. The alg-1(anti) mutations broadly impair the function of many microRNAs and cause dosage-dependent phenotypes that are more severe than the complete loss of ALG-1. ALG-1(anti) mutant proteins are competent for promoting Dicer cleavage of microRNA precursors and for associating with and stabilizing microRNAs. However, our results suggest that ALG-1(anti) proteins may sequester microRNAs in immature and functionally deficient microRNA Induced Silencing Complexes (miRISCs), and hence compete with ALG-2 for access to functional microRNAs. Immunoprecipitation experiments show that ALG-1(anti) proteins display an increased association with Dicer and a decreased association with AIN-1/GW182. These findings suggest that alg-1(anti) mutations impair the ability of ALG-1 miRISC to execute a transition from Dicer-associated microRNA processing to AIN-1/GW182 associated effector function, and indicate an active role for ALG/Argonaute in mediating this transition. |
| 巻・号 | 10(4) |
| ページ | e1004286 |
| 公開日 | 2014-4-1 |
| DOI | 10.1371/journal.pgen.1004286 |
| PII | PGENETICS-D-13-02937 |
| PMID | 24763381 |
| PMC | PMC3998888 |
| MeSH | Alleles Amino Acid Sequence Animals Argonaute Proteins / genetics* Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Carrier Proteins / genetics* Conserved Sequence Gene Expression Regulation, Developmental / genetics MicroRNAs / genetics* Molecular Sequence Data Mutation / genetics* Repressor Proteins / genetics Sequence Alignment |
| IF | 5.175 |
| 引用数 | 14 |
| 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 | tm492 tm369 tm4566 |