Biogenesis and regulation of the let-7 miRNAs and their functional implications.
10.1007/s13238-015-0212-y
- Author:
Hosuk LEE
1
;
Sungwook HAN
1
;
Chang Seob KWON
2
;
Daeyoup LEE
3
Author Information
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.
3. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea. daeyoup@kaist.ac.kr.
- Publication Type:Journal Article
- Keywords:
LIN28A/B;
TUTase;
let-7 family;
miRNA biogenesis;
miRNA processing
- MeSH:
Animals;
Base Sequence;
Gene Expression Regulation;
Humans;
MicroRNAs;
biosynthesis;
chemistry;
genetics;
metabolism;
RNA Processing, Post-Transcriptional;
RNA Stability;
Transcription, Genetic
- From:
Protein & Cell
2016;7(2):100-113
- CountryChina
- Language:English
-
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.
