Selective blockade of MicroRNA processing by Lin28

被引：1147

作者：

Viswanathan, Srinivas R. ^{[1
]}

Daley, George Q. ^{[1
,2
,3
,4
]}

Gregory, Richard I. ^{[1
]}

机构：

[1] Harvard Univ, Childrens Hosp Boston, Dept Biol Chem & Mol Pharmacol, Stem Cell Program,Sch Med,Harvard Stem Cell Inst, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Div Pediat Hematol Oncol, Childrens Hosp Boston, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Howard Hughes Med Inst, Div Hematol, Boston, MA 02115 USA

来源：

SCIENCE | 2008年 / 320卷 / 5872期

关键词：

D O I：

10.1126/science.1154040

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

MicroRNAs ( miRNAs) play critical roles in development, and dysregulation of miRNA expression has been observed in human malignancies. Recent evidence suggests that the processing of several primary miRNA transcripts (pri- miRNAs) is blocked posttranscriptionally in embryonic stem cells, embryonal carcinoma cells, and primary tumors. Here we show that Lin28, a developmentally regulated RNA binding protein, selectively blocks the processing of pri- let- 7 miRNAs in embryonic cells. Using in vitro and in vivo studies, we found that Lin28 is necessary and sufficient for blocking Microprocessor- mediated cleavage of pri- let- 7 miRNAs. Our results identify Lin28 as a negative regulator of miRNA biogenesis and suggest that Lin28 may play a central role in blocking miRNA-mediated differentiation in stem cells and in certain cancers.

引用

页码：97 / 100

页数：4

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