Loss of individual microRNAs causes mutant phenotypes in sensitized genetic backgrounds in C. elegans.
Loss of individual microRNAs causes mutant phenotypes in sensitized genetic backgrounds in C. elegans.
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DOI：
10.1016/j.cub.2010.05.062
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发表时间：
2010-07-27
期刊：
影响因子：
9.2
通讯作者：
Abbott, Allison L.
中科院分区：
文献类型：
--
作者：
Brenner, John L.;Jasiewicz, Kristen L.;Fahley, Alisha F.;Kemp, Benedict J.;Abbott, Allison L.
microrna （mirna）是一种小的非编码rna，可调节其mRNA靶标的翻译和/或稳定性。先前的研究表明，对于秀丽隐杆线虫的大多数miRNA基因，单基因敲除不会导致可检测的突变表型。这可能部分归因于mirna之间的功能冗余。然而，在大多数情况下，携带miRNA家族所有成员缺失的蠕虫不会表现出强烈的突变表型。它们可能与不相关的mirna或非mirna基因一起在调控网络中发挥作用，可能是为了确保发育机制的稳健性。为了验证这一点，我们研究了在基因敏感背景下缺乏单个mirna的蠕虫。这些包括所有mirna加工和活性降低的遗传背景，或一系列调控途径活性降低的遗传背景。使用这两种方法，在本分析中包含的31个mirna中鉴定了25个突变表型。我们的研究结果描述了单个miRNA的生物学作用，并表明使用敏化遗传背景为miRNA功能分析提供了一种有效的方法。
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the translation and/or the stability of their mRNA targets. Previous work showed that for most miRNA genes of C. elegans, single gene knockouts did not result in detectable mutant phenotypes. This may be due, in part, to functional redundancy between miRNAs. However, in most cases, worms carrying deletions of all members of a miRNA family do not display strong mutant phenotypes. They may function together with unrelated miRNAs or with non-miRNA genes in regulatory networks, possibly to ensure the robustness of developmental mechanisms. To test this, we examined worms lacking individual miRNAs in genetically sensitized backgrounds. These include genetic backgrounds with reduced processing and activity of all miRNAs or with reduced activity of a wide array of regulatory pathways. Using these two approaches, mutant phenotypes were identified for 25 out of 31 miRNAs included in this analysis. Our findings describe biological roles for individual miRNAs and suggest that use of sensitized genetic backgrounds provides an efficient approach for miRNA functional analysis.
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