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

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



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.



Chendrimada, T.P., Gregory, R.I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., and Shiekhattar, R. (2005). TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436, 740–744.

Dangi-Garimella, S., Yun, J., Eves, E.M., Newman, M., Erkeland, S.J., Hammond, S.M., Minn, A.J., and Rosner, M.R. (2009). Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. EMBO J. 28, 347–358.