Biogenesis and regulation of the let-7 miRNAs and their functional implications. Issue 2 (23rd September 2015)

• Record Type: Journal Article
• Authors: Lee, Hosuk; Han, Sungwook; Kwon, Chang Seob; Lee, Daeyoup
• Is Part Of: Protein & cell. Volume 7:Issue 2(2016)
• Page Start: 100
• Page End: 113
• Publication Date: 2015-09-23
• Subjects: miRNA processing -- miRNA biogenesis -- let-7 family -- TUTase -- LIN28A/B; Proteins -- Periodicals; Cells -- Periodicals; Cytology -- Periodicals; 572.6
• DOI: 10.1007/s13238-015-0212-y
• Languages: English
• ISSNs: 1674-800X

Abstract

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.