Phosphorylation of the human microRNA-generating complex mediates MAPK/Erk signaling (Cell, 2009, 139:112-122)

報告日期: 2010/04/20
報告時間: 15:10/16:00
報告學生: 黃苑清
講評老師: 呂佩融
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990427-1.pdf

Phosphorylation of the Human MicroRNA-Generating Complex

Mediates MAPK/Erk Signaling

Zain Paroo, Xuecheng Ye, She Chen, and Qinghua Liu1,

Cell 139, 112–122, October 2, 2009

 

SpeakerYuan-Ching Huang (黃苑清)

CommentatorLu, Pei-Jung Ph.D (呂佩融老師)

Time2010-04-20() 15:10-16:00

 

Abstract

MicroRNAs (miRNAs) are small (16 to 29 nucleotides) noncoding RNA molecules. Long primary miRNA transcripts (pri-miRNAs) are generally transcribed by RNA polymerase II (Pol II) in the nucleus and are processed by the RNase III enzyme Drosha into 65 nt stem-loop structures known as precursor miRNAs (pre-miRNAs). The dsRNA-binding protein exportin 5 then transports the pre-miRNA into the cytoplasm in a Ran-GTP-dependent manner where Dicer and its dsRNA-binding protein partners, HIV TAR RNA-binding protein (TRBP) and protein activator of protein kinase PKR (PACT) process the pre-miRNA and load the 22 nt mature miRNA into RISC . The mature miRNA binds to its target mRNA 3'UTR through Argonaute-RISC effector complexes, that complexes direct translational repression and subsequent mRNA degradation to silence gene expression. The miRNA-generating complex consists of the ribonuclease III Dicer and a partner double-strand RNA-binding protein (dsRBP). In humans, Dicer is accompanied by TRBP. Expression of phospho-mimic TRBP and TRBP phosphorylation is regulated by MAPK/Erk. TRBP phosphorylation stabilizes the miRNA-generating complex and increases microRNA products and silencing. Serum and tumor promoter PMA activates MKK1/Erk, which enhances miRNA pathway activity in a phospho-TRBP-dependent manner. These effects were accompanied increasing in levels of growth-promoting miRNA and reduced expression of let-7 tumor suppressor miRNA. These studies indicate that the MAPK/Erk signaling phophorylates the miRNA-generating complex and targets the miRNA pathway to regulate biological responses.

 

References

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