| 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
|
| リソース情報 |
| 線虫 |
tm492
tm369
tm4566 |
