RACK-1 regulates let-7 microRNA expression and terminal cell differentiation in Caenorhabditis elegans.
RACK-1 regulates let-7 microRNA expression and terminal cell differentiation in Caenorhabditis elegans.
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DOI：
10.4161/cc.29017
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Chan SP
中科院分区：
文献类型：
--
作者：
Chu YD;Wang WC;Chen SA;Hsu YT;Yeh MW;Slack FJ;Chan SP
let-7 microRNA （miRNA）在秀丽隐杆线虫异慢性基因通路中调控细胞周期退出和终末分化。let-7的低表达导致秀丽隐杆线虫的外阴和皮下细胞发育迟缓，并与几种人类癌症有关。此前，活化C激酶1的多功能支架蛋白受体（RACK1）被提出用于促进miRNA诱导的沉默复合体（miRISC）募集到多聚体，并且是秀丽隐杆线虫和人类miRNA功能所必需的。在这里，我们发现通过RNAi消耗秀丽隐杆线虫的RACK-1增加了let-7 miRNA水平，并抑制了携带半形let-7（n2853）等位基因或缺乏let-7家族miRNA基因mir-48和mir-241的突变体的外侧皮下缝细胞的末端分化迟缓。RACK-1的缺失也会增加前体let-7 miRNA的水平。当Dicer被敲低，pre-miRNA加工被抑制时，RACK-1的缺失仍然会导致pre-let-7水平升高，这表明RACK-1影响了Dicer上游的生物发生机制。let-7启动子活性或初级let-7 miRNA水平的变化与rack1的缺失无关，这表明rack1在转录后水平影响了let-7 miRNA的生物发生。有趣的是，rack-1敲低也会增加其他一些前体mirna的水平。我们的研究结果表明，RACK-1控制了包括let-7在内的一个mirna子集的生物发生，并以这种方式在秀丽隐杆线虫发育过程中的异慢性基因途径中发挥作用。
The let-7 microRNA (miRNA) regulates cell cycle exit and terminal differentiation in the C. elegans heterochronic gene pathway. Low expression of let-7 results in retarded vulva and hypodermal cell development in C. elegans and has been associated with several human cancers. Previously, the versatile scaffold protein receptor for activated C kinase 1 (RACK1) was proposed to facilitate recruitment of the miRNA-induced silencing complex (miRISC) to the polysome and to be required for miRNA function in C. elegans and humans. Here, we show that depletion of C. elegans RACK-1 by RNAi increases let-7 miRNA levels and suppresses the retarded terminal differentiation of lateral hypodermal seam cells in mutants carrying the hypomorphic let-7(n2853) allele or lacking the let-7 family miRNA genes mir-48 and mir-241. Depletion of RACK-1 also increases the levels of precursor let-7 miRNA. When Dicer is knocked down and pre-miRNA processing is inhibited, depletion of RACK-1 still leads to increased levels of pre-let-7, suggesting that RACK-1 affects a biogenesis mechanism upstream of Dicer. No changes in the activity of the let-7 promoter or the levels of primary let-7 miRNA are associated with depletion of RACK-1, suggesting that RACK-1 affects let-7 miRNA biogenesis at the post-transcriptional level. Interestingly, rack-1 knockdown also increases the levels of a few other precursor miRNAs. Our results reveal that RACK-1 controls the biogenesis of a subset of miRNAs, including let-7, and in this way plays a role in the heterochronic gene pathway during C. elegans development.
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DOI：
10.4161/cc.7.19.6778
发表时间：
2008-10
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Ding XC;Slack FJ;Grosshans H
通讯作者：
Grosshans H
DOI：
10.1073/pnas.76.3.1333
发表时间：
1979-01-01
影响因子：
11.1
作者：
EMMONS, SW;KLASS, MR;HIRSH, D
通讯作者：
HIRSH, D
影响因子：
4
作者：
Ambros, Victor
通讯作者：
Ambros, Victor
影响因子：
4.5
作者：
Chan, Shih-Peng;Ramaswamy, Gopalakrishna;Slack, Frank J.
通讯作者：
Slack, Frank J.
影响因子：
64.5
作者：
Diederichs, Sven;Haber, Daniel A.
通讯作者：
Haber, Daniel A.