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

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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.
Publisher
Springer Verlag
Issue Date
2016-02
Language
English
Article Type
Review
Keywords

EMBRYONIC STEM-CELLS; SMALL TEMPORAL RNAS; MICRORNA BIOGENESIS; CAENORHABDITIS-ELEGANS; C-ELEGANS; POSTTRANSCRIPTIONAL REGULATION; NUCLEAR EXPORT; SELF-RENEWAL; HUMAN DICER; DROSOPHILA-MELANOGASTER

Citation

PROTEIN & CELL, v.7, no.2, pp.100 - 113

ISSN
1674-800X
DOI
10.1007/s13238-015-0212-y
URI
http://hdl.handle.net/10203/208676
Appears in Collection
BS-Journal Papers(저널논문)
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