Selective Blockade of MicroRNA Processing by Lin28 | Zendy

Srinivas R. Viswanathan | Zendy; George Q. Daley | Zendy; Richard I. Gregory | Zendy

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Selective Blockade of MicroRNA Processing by Lin28

Author(s) -

Srinivas R. Viswanathan,

George Q. Daley,

Richard I. Gregory

Publication year - 2008

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.1154040

Subject(s) - lin28 , microrna , embryonic stem cell , biology , biogenesis , microbiology and biotechnology , stem cell , negative regulator , cancer research , genetics , induced pluripotent stem cell , gene , signal transduction

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.

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