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Posttranscriptional crossregulation between Drosha and DGCR8.

作者信息

Han Jinju, Pedersen Jakob S, Kwon S Chul, Belair Cassandra D, Kim Young-Kook, Yeom Kyu-Hyeon, Yang Woo-Young, Haussler David, Blelloch Robert, Kim V Narry

机构信息

School of Biological Sciences and National Creative Research Center, Seoul National University, Seoul 151-742, Korea.

出版信息

Cell. 2009 Jan 9;136(1):75-84. doi: 10.1016/j.cell.2008.10.053.


DOI:10.1016/j.cell.2008.10.053
PMID:19135890
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2680683/
Abstract

The Drosha-DGCR8 complex, also known as Microprocessor, is essential for microRNA (miRNA) maturation. Drosha functions as the catalytic subunit, while DGCR8 (also known as Pasha) recognizes the RNA substrate. Although the action mechanism of this complex has been intensively studied, it remains unclear how Drosha and DGCR8 are regulated and if these proteins have any additional role(s) apart from miRNA processing. Here, we report that Drosha and DGCR8 regulate each other posttranscriptionally. The Drosha-DGCR8 complex cleaves the hairpin structures embedded in the DGCR8 mRNA and thereby destabilizes the mRNA. We further find that DGCR8 stabilizes the Drosha protein via protein-protein interaction. This crossregulation between Drosha and DGCR8 may contribute to the homeostatic control of miRNA biogenesis. Furthermore, microarray analyses suggest that a number of mRNAs may be downregulated in a Microprocessor-dependent, miRNA-independent manner. Our study reveals a previously unsuspected function of Microprocessor in mRNA stability control.

摘要

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本文引用的文献

[1]
Embryonic stem cell-specific microRNAs regulate the G1-S transition and promote rapid proliferation.

Nat Genet. 2008-12

[2]
Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs.

Genes Dev. 2008-10-15

[3]
Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model.

Nat Genet. 2008-6

[4]
Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression.

Proc Natl Acad Sci U S A. 2008-4-29

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Nat Biotechnol. 2008-4

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Genome Res. 2008-4

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Brain Pathol. 2008-1

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Nat Rev Genet. 2008-2

[10]
MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle.

Endocr Relat Cancer. 2007-9

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