Biogenesis and regulation of the let-7 miRNAs and their functional implications

• 出版年: Protein & Cell
• 主要な著者: Hosuk Lee, Sungwook Han, Chang Seob Kwon, Daeyoup Lee
• フォーマット: 論文
• 言語: 英語
• 出版事項: Oxford University Press 2015-09-01
• 主題: miRNA processing; miRNA biogenesis; let-7 family; TUTase; LIN28A/B
• オンライン･アクセス: http://link.springer.com/article/10.1007/s13238-015-0212-y
• ISSN: 1674-800X; 1674-8018

ABSTRACT The let-7 miRNA was one of the first miRNAs discovered in the nematode, Caenorhabditis elegans, and its biological functions show a high level of evolutionary conservation from the nematode to the human. Unlike in C. elegans, higher animals have multiple isoforms of let-7 miRNAs; these isoforms share a consensus sequence called the ‘seed sequence’ and these isoforms are categorized into let-7 miRNA family. The expression of let-7 family is required for developmental timing and tumor suppressor function, but must be suppressed for the self-renewal of stem cells. Therefore, let-7 miRNA biogenesis must be carefully controlled. To generate a let-7 miRNA, a primary transcript is produced by RNA polymerase II and then subsequently processed by Drosha/DGCR8, TUTase, and Dicer. Because dysregulation of let-7 processing is deleterious, biogenesis of let-7 is tightly regulated by cellular factors, such as the RNA binding proteins, LIN28A/B and DIS3L2. In this review, we discuss the biological functions and biogenesis of let-7 miRNAs, focusing on the molecular mechanisms of regulation of let-7 biogenesis in vertebrates, such as the mouse and the human.