Uncoupling of lin-14 mRNA and protein repression by nutrient deprivation in Caenorhabditis elegans
Uncoupling of lin-14 mRNA and protein repression by nutrient deprivation in Caenorhabditis elegans
复制标题
DOI：
10.1261/rna.1258309
复制
发表时间：
2009-03-01
期刊：
影响因子：
4.5
通讯作者：
Pasquinelli, Amy E.
中科院分区：
文献类型：
--
作者：
Holtz, Janette;Pasquinelli, Amy E.
在动物中，microRNA（miRNAs）通常与靶基因的3 '-非翻译区（3' UTR）中的部分互补位点配对。miRNAs的调节通常导致靶mRNA和蛋白质表达的下调，其机制尚未完全阐明。此外，环境条件的变化已被证明会影响某些细胞培养系统中的miRNA功能。在这里，我们报告了营养剥夺对发育中蠕虫内源性miRNA靶点调节的影响。在秀丽隐杆线虫中，lin-4 miRNA识别lin-14 3 'UTR中的多个位点，并指导mRNA降解和翻译抑制，但尚不清楚这些过程是如何耦合的。在这项研究中，我们证明，营养剥夺的结果在lin-14 mRNA的损失，但不是蛋白质，镇压。在从进食条件下移除的蠕虫中，lin-14 mRNA重新积累，尽管lin-4 miRNA继续表达。在缺乏lin-4 miRNA或lin-14 3 'UTR靶位点的遗传突变体中，营养剥夺期间lin-14 mRNA水平的相对增加不太明显。总之，lin-14在mRNA和蛋白质水平的调节可以通过培养条件的变化来解偶联，表明miRNA功能可以通过多细胞生物中的环境来调节。认识到内源性miRNA途径可能对环境敏感是阐明miRNA用于调节靶mRNA和蛋白质表达的机制的重要考虑因素。
`In animals, microRNAs (miRNAs), typically, pair to sites of partial complementarity in the 3'-untranslated regions (3'UTRs) of target genes. Regulation by miRNAs often results in down-regulation of target mRNA and protein expression by mechanisms that are yet to be fully elucidated. Additionally, changes in environmental conditions have been shown to influence miRNA function in some cell culture systems. Here, we report the effect of nutrient deprivation on regulation of an endogenous miRNA target in developing worms. In Caenorhabditis elegans, the lin-4 miRNA recognizes multiple sites in the lin-14 3'UTR and directs mRNA degradation and translational repression, but it is unclear how these processes are coupled. In this study, we demonstrate that nutrient deprivation results in loss of lin-14 mRNA, but not protein, repression. In worms removed from feeding conditions, lin-14 mRNA reaccumulates despite the continued expression of lin-4 miRNA. The relative increase in lin-14 mRNA levels during nutrient deprivation is less pronounced in genetic mutants lacking lin-4 miRNA or the lin-14 3'UTR target sites. In conclusion, regulation of lin-14 at the mRNA and protein levels can be uncoupled by changes in culture conditions, indicating that miRNA function can be modulated by environment in multicellular organisms. The awareness that endogenous miRNA pathways can be sensitive to environment is an important consideration for elucidating the mechanism used by miRNAs to regulate target mRNA and protein expression.