title: Biogenesis and regulation of the let-7 miRNAs and their functional implications.
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.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea.
authors.forename: Hosuk
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea.
authors.forename: Sungwook
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Chemistry and Biology, Korea Science Academy of KAIST, Busan, 614-822, Korea.
authors.forename: Chang Seob
authors.initials: CS
authors.lastname: Kwon
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea. daeyoup@kaist.ac.kr.
authors.forename: Daeyoup
authors.initials: D
authors.lastname: Lee
mesh_terms: D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs
keywords: LIN28A/B; TUTase; let-7 family; miRNA biogenesis; miRNA processing