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Tytuł pozycji:

MicroRNA-Independent Modulation of DICER1 Expression by hAgo2.

Tytuł:
MicroRNA-Independent Modulation of DICER1 Expression by hAgo2.
Autorzy:
Yang CH; Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Li HC; Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien, Taiwan.
Ku TS; Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan.
Wu CH; Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan.
Sim KC; Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan.
Lo SY; Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan .; Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan.; Department of Laboratory Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
Źródło:
Molecular and cellular biology [Mol Cell Biol] 2020 Sep 28; Vol. 40 (20). Date of Electronic Publication: 2020 Sep 28 (Print Publication: 2020).
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Publication: 2023- : [Philadelphia] : Taylor & Francis
Original Publication: [Washington, D.C.] : American Society for Microbiology, [c1981-
MeSH Terms:
Argonaute Proteins/*genetics
DEAD-box RNA Helicases/*genetics
Gene Expression Regulation, Neoplastic/*genetics
MicroRNAs/*genetics
Neoplasms/*genetics
Ribonuclease III/*genetics
3' Untranslated Regions/genetics ; A549 Cells ; Argonaute Proteins/metabolism ; Binding Sites/genetics ; CRISPR-Cas Systems ; Cell Line, Tumor ; DEAD-box RNA Helicases/metabolism ; HEK293 Cells ; HeLa Cells ; Heterogeneous Nuclear Ribonucleoprotein D0/genetics ; Heterogeneous Nuclear Ribonucleoprotein D0/metabolism ; Humans ; RNA Interference ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Ribonuclease III/metabolism
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Contributed Indexing:
Keywords: coimmunoprecipitation; knockdown; knockout; luciferase reporter assay; posttranscriptional level
Substance Nomenclature:
0 (3' Untranslated Regions)
0 (AGO2 protein, human)
0 (Argonaute Proteins)
0 (HNRNPD protein, human)
0 (Heterogeneous Nuclear Ribonucleoprotein D0)
0 (MicroRNAs)
0 (RNA, Messenger)
0 (RNA, Small Interfering)
EC 3.1.26.3 (DICER1 protein, human)
EC 3.1.26.3 (Ribonuclease III)
EC 3.6.4.13 (DEAD-box RNA Helicases)
Entry Date(s):
Date Created: 20200812 Date Completed: 20201021 Latest Revision: 20210328
Update Code:
20240105
PubMed Central ID:
PMC7523658
DOI:
10.1128/MCB.00221-20
PMID:
32778571
Czasopismo naukowe
Many proteins, including DICER1 and hAgo2, are involved in the biogenesis of microRNAs (miRNAs). Whether hAgo2 regulates DICER1 expression is unknown. Exogenously overexpressed hAgo2 suppressed DICER1 expression at the levels of both protein and mRNA, and the reduction in hAgo2 expression enhanced DICER1 expression. Precursor miRNA processing mediated by DICER1 was also modulated by hAgo2. However, hAgo2 protein did not suppress DICER1 promoter activity. Therefore, hAgo2 protein probably regulates DICER1 expression at the posttranscriptional level. Indeed, hAgo2 protein inhibited the reporter assay of the DICER1 mRNA 3' untranslated region (3'-UTR). Previous reports have demonstrated that miRNAs (e.g., let-7 and miR-103/107) inhibited DICER1 expression posttranscriptionally. However, hAgo2 still suppressed DICER1 expression in the cells depleted of these miRNAs. Moreover, the reporter activities of the DICER1 mRNA 3'-UTR without these miRNA binding sites were still suppressed by hAgo2. Therefore, in addition to an miRNA-dependent pathway, hAgo2 can also modulate DICER1 expression through an miRNA-independent mechanism. Downregulation of DICER1 expression was further proven to be dependent on both hAgo2 and AUF1 proteins. Interactions of hAgo2 and AUF1 proteins were demonstrated by the coimmunoprecipitation assay. As expected, hAgo2 could not suppress the DICER1 mRNA 3'-UTR reporter with a mutation in the potential AUF1-binding site. Thus, downregulation of DICER1 expression through the 3'-UTR requires both hAgo2 and AUF1.
(Copyright © 2020 American Society for Microbiology.)

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