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Smad Proteins Bind a Conserved RNA Sequence to Promote MicroRNA Maturation by Drosha
Open accessAbstract
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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Cites
The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a
Guil, S., & Cáceres, J. F. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1250 · Cited by 567
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O'Connell, R. M., Rao, D. S., & Baltimore, D. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075013 · Cited by 843
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Zhang, Y., Alexander, P. B., & Wang, X.-F. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022145 · Cited by 626
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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- Davis, B. N., Hilyard, A. C., Nguyen, P. H., Lagna, G., & Hata, A. (2010). Smad Proteins Bind a Conserved RNA Sequence to Promote MicroRNA Maturation by Drosha. Molecular Cell. https://doi.org/10.1016/j.molcel.2010.07.011
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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