SMAD proteins control DROSHA-mediated microRNA maturation (Nature, 2008, 454:56-61)

報告日期: 2009/04/28
報告時間: 17:05/17:55
報告學生: 郭怡孜
講評老師: 劉校生
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980421-3.pdf

SMAD proteins control DROSHA mediated microRNA maturation

 

Brandi N. Davis, Aaron C. Hilyard, Giorgio Lagna & Akiko Hata

 

NATURE, July 2008, Vol.454, p.56-63

 

Speaker : Yi-Zih Kuo (郭怡孜)

Commentator : Hsiao-Sheng Liu(劉校生)

Date : 2009/4/28 17:10-18:00

Room : 602

 

Abstract

MicroRNAs (miRNAs), small non-coding RNAs, are important regulators of gene expression that control both physiological and pathological processes such as vascular development and cancer1. Transform growth factor-b (TGF-b) superfamily of growth factors directs vascular development and homeostasis, including induction of the contractile phenotype in human vascular smooth muscle cells (VSMCs)2. The involvement of miRNAs in the TGF-b-family mediated modulation of the VSMC phenotype remains unexplored. Author use quantitative polymerase chain reaction with reverse transcription (qRT–PCR) to find that miR-21 and miR-199a showed a significant increase in expression in TGF-b-family mediated VSMCs, and explored that miR-21 modulates SMC differentiation by TGF-b-family signaling by neutralizing miR-21 function using 20-O-methyl antagomirs. Because miR-21 has been shown to target the tumour suppressor gene PDCD4 (programmed cell death 4), they also proved that PDCD4 is a critical target of miR-21 in vascular smooth muscle. Next, they looked at which step of miR-21 biogenesis was affected by TGF-b-family signalling, they found the levels of pri-miR-21 unchanged, suggesting that signaling was affecting miR-21 expression posttranscriptionally. In previous study indicated that TGF-b-family transduce their signal through receptor-mediated phosphorylation of cytoplasmic SMAD proteins. To elucidate the potential role of SMADs in miR-21 induction, they used RNAi knockdown technique to show ligand-specific SMAD proteins bind to the DROSHA microprocessor subunit p68 to facilitate pre-miRNA accumulation and the shared cofactor SMAD4 is not required for miR-21 maturation process. In addition, this study also indicated that TGF-b-family increases miR-21 expression in breast carcinoma. The study expands our understanding of miRNA biogenesis and maturation, elucidating a mechanism by which extracellular signaling directs cell differentiation via posttranscriptional regulation of miRNA expression.

 

Reference

1.  Elizabeth Scalbert and Antoine Bril, Implication of microRNAs in the cardiovascular system. Current Opinion in Pharmacology 2008, 8:181–188

2.  ten Dijke, P. & Arthur, H. M. Extracellular control of TGFb signalling in vascular development and disease. Nature Rev. Mol. Cell Biol. 2007, 8, 857–868.