PTEN modulates miR-21 processing via RNA-regulatory protein RNH1.
PTEN modulates miR-21 processing via RNA-regulatory protein RNH1.
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DOI：
10.1371/journal.pone.0028308
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kim JH
中科院分区：
文献类型：
--
作者：
Kim YJ;Park SJ;Choi EY;Kim S;Kwak HJ;Yoo BC;Yoo H;Lee SH;Kim D;Park JB;Kim JH
Aberrant miR-21 expression is closely associated with cell proliferation, anti-apoptosis, migration, invasion, and metastasis in various cancers. However, the regulatory mechanism of miR-21 biogenesis is largely unknown. Here, we demonstrated that the tumor suppressor PTEN negatively regulates the expression of oncogenic miR-21 at the post-transcriptional level. Moreover, our results suggest that PTEN plays such a role through the indirect interaction with the Drosha complex. To elucidate how PTEN regulates pri- to pre-miR-21 processing, we attempted to find PTEN-interacting proteins and identified an RNA-regulatory protein, RNH1. Using the sensor to monitor pri-miR-21 processing, we demonstrated that RNH1 is necessary and sufficient for pri-miR-21 processing. Moreover, our results propose that the nuclear localization of RNH1 is important for this function. Further analysis showed that RNH1 directly interacts with the Drosha complex and that PTEN blocks this interaction. Taken together, these results suggest that the PTEN-mediated miR-21 regulation is achieved by inhibiting the interaction between the Drosha complex and RNH1, revealing previously unidentified role of PTEN in the oncogenic miR-21 biogenesis.
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