REVIEW

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

  • Hosuk Lee 1 ,
  • Sungwook Han 1 ,
  • Chang Seob Kwon 2 ,
  • Daeyoup Lee , 1
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  • 1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea
  • 2. Department of Chemistry and Biology, Korea Science Academy of KAIST, Busan 614-822, Korea

Received date: 15 Jul 2015

Accepted date: 17 Aug 2015

Published date: 13 Mar 2016

Copyright

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The let-7 miRNAwasone of thefirstmiRNAsdiscovered 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.

Cite this article

Hosuk Lee , Sungwook Han , Chang Seob Kwon , Daeyoup Lee . Biogenesis and regulation of the let-7 miRNAs and their functional implications[J]. Protein & Cell, 2016 , 7(2) : 100 -113 . DOI: 10.1007/s13238-015-0212-y

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