The mir-51 family of microRNAs functions in diverse regulatory pathways in Caenorhabditis elegans.
The mir-51 family of microRNAs functions in diverse regulatory pathways in Caenorhabditis elegans.
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DOI：
10.1371/journal.pone.0037185
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Abbott AL
中科院分区：
文献类型：
--
作者：
Brenner JL;Kemp BJ;Abbott AL
mir-51家族的microRNAs（miRNAs）在C.线虫是高度保守的miR-99/100家族的一部分。而C. elegans导致胚胎死亡，单个miR-51家族成员的丧失导致与ALG-1丧失相关的发育时间延迟缺陷的抑制。这种抑制发育时间缺陷的机制尚不清楚。为了解决这个问题，我们的特点的mir-51家族的功能，在发育时序途径。我们进行了遗传分析，并确定mir-51家族成员调节hbl-1上游L2阶段的发育时序途径。mir-51家族成员mir-52的缺失抑制了与let-7家族成员和lin-46缺失相关的发育迟缓的时间缺陷。在lin-14、hbl-1和mir-48（ve 33）中观察到早熟缺陷的增强，但在发育定时基因中没有发现。有趣的是，mir-51家族成员显示出与其他miRNA调节途径的遗传相互作用，这些途径由let-7和mir-35家族miRNA、lsy-6、miR-240/786和miR-1调节。mir-52的缺失可能不会通过增加miRNA生物合成或miRNA活性来抑制miRNA调节的途径。我们发现，在mir-52或mir-52/53/54/55/56突变体蠕虫中，let-7、miR-58、miR-62或miR-244四种成熟miRNA的水平没有增加。此外，我们观察到在缺少mir-52的蠕虫子宫细胞中异位lsy-6抑制下游靶点的活性没有增加。我们认为，mir-51家族通过在C.优美的
The mir-51 family of microRNAs (miRNAs) in C. elegans are part of the deeply conserved miR-99/100 family. While loss of all six family members (mir-51-56) in C. elegans results in embryonic lethality, loss of individual mir-51 family members results in a suppression of retarded developmental timing defects associated with the loss of alg-1. The mechanism of this suppression of developmental timing defects is unknown. To address this, we characterized the function of the mir-51 family in the developmental timing pathway. We performed genetic analysis and determined that mir-51 family members regulate the developmental timing pathway in the L2 stage upstream of hbl-1. Loss of the mir-51 family member, mir-52, suppressed retarded developmental timing defects associated with the loss of let-7 family members and lin-46. Enhancement of precocious defects was observed for mutations in lin-14, hbl-1, and mir-48(ve33), but not later acting developmental timing genes. Interestingly, mir-51 family members showed genetic interactions with additional miRNA-regulated pathways, which are regulated by the let-7 and mir-35 family miRNAs, lsy-6, miR-240/786, and miR-1. Loss of mir-52 likely does not suppress miRNA-regulated pathways through an increase in miRNA biogenesis or miRNA activity. We found no increase in the levels of four mature miRNAs, let-7, miR-58, miR-62 or miR-244, in mir-52 or mir-52/53/54/55/56 mutant worms. In addition, we observed no increase in the activity of ectopic lsy-6 in the repression of a downstream target in uterine cells in worms that lack mir-52. We propose that the mir-51 family functions broadly through the regulation of multiple targets, which have not yet been identified, in diverse regulatory pathways in C. elegans.
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