https://scholars.lib.ntu.edu.tw/handle/123456789/384864
標題: | RACK-1 regulates let-7 microRNA expression and terminal cell differentiation in Caenorhabditis elegans | 作者: | Yi, Yung-Hsiang Ma, Tian-Hsiang Lee, Li-Wei Chiou, Pey-Tsyr Chen, Po-Hsiang Lee, Ching-Ming Chu, Yu-De Yu, Hsiang Hsiung, Kuei-Ching Tsai, Yi-Tzang Lee, Chi-Chang Chang, Yu-Sun SHIH-PENG CHAN Tan, Bertrand Chin-Ming |
關鍵字: | Caenorhabditis elegans; Heterochronic; Let -7; MicroRNA; RACK1 | 公開日期: | 2014 | 卷: | 13 | 期: | 12 | 起(迄)頁: | 1995-2009 | 來源出版物: | Cell Cycle | 摘要: | 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. ? 2014 Landes Bioscience. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84902437111&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/384864 |
DOI: | 10.4161/cc.29017 | SDG/關鍵字: | let 7 microRNA; microRNA; receptor for activated C kinase 1; unclassified drug; argonaute protein; Caenorhabditis elegans protein; cell receptor; let-7 microRNA, C elegans; microRNA; RACK-1 protein, C elegans; ribonuclease III; allele; article; biogenesis; Caenorhabditis elegans; cell differentiation; cell division; cell maturation; cell proliferation; controlled study; gene control; gene expression; gene silencing; larval stage; lethality; loss of function mutation; male; nonhuman; phenotype; protein depletion; protein expression; RNA interference; RNA processing; animal; Caenorhabditis elegans; cytology; genetics; metabolism; mutation; Animals; Argonaute Proteins; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Differentiation; MicroRNAs; Mutation; Receptors, Cytoplasmic and Nuclear; Ribonuclease III; RNA Interference |
顯示於: | 醫學系 |
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