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Cited by 383

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Smad Proteins Bind a Conserved RNA Sequence to Promote MicroRNA Maturation by Drosha

Open access
Davis, Brandi N., Hilyard, Aaron C., Nguyen, Peter H., Lagna, Giorgio, Hata, Akiko·2010·Molecular Cell

Abstract

Summary The signal transducers of the Transforming Growth Factor β (TGFβ)/Bone Morphogenetic Protein (BMP), the Smads, promote the expression of a subset of miRNAs by facilitating the cleavage reaction by Drosha. The mechanism that limits Smad-mediated processing to a selective group of miRNAs remained hitherto unexplored. In this study, we expand the number of TGFβ/BMP-regulated miRNAs (T/B-miRs) to 20. Interestingly, a majority of T/B-miRs contain a consensus sequence (R-SBE) within the stem region of the primary transcripts of T/B-miRs (pri-T/B-miRs). Here, we demonstrate that Smads directly bind the R-SBE. Mutation of the R-SBE abrogates TGFβ/BMP-induced recruitment of Smads, Drosha, and DGCR8 to pri-T/B-miRs, and impairs their processing, while introduction of R-SBE to unregulated pri-miRNAs is sufficient to recruit Smads and allow regulation by TGFβ/BMP. Thus, Smads are multifunctional proteins which modulate gene expression transcriptionally through DNA binding, and post-transcriptionally by pri-miRNA binding and regulation of miRNA processing.

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Crossref · 10.1016/j.molcel.2010.07.011

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Metadata

Authors
Davis, B. N., Hilyard, A. C., Nguyen, P. H., Lagna, G., & Hata, A.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2010-08
Volume
39
Issue
3
Pages
373-384
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2007701028
Cited by
383
References
1
FWCI
12.19
Type
journal article
Language
en
Open access
bronze

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