title: PTEN modulates miR-21 processing via RNA-regulatory protein RNH1.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Youn-Jae
authors.initials: YJ
authors.lastname: Kim
authors.forename: Se-Jeong
authors.initials: SJ
authors.lastname: Park
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Sol
authors.initials: S
authors.lastname: Kim
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kwak
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Heon
authors.initials: H
authors.lastname: Yoo
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Daesoo
authors.initials: D
authors.lastname: Kim
authors.forename: Jong Bae
authors.initials: JB
authors.lastname: Park
authors.forename: Jong Heon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D035683:MicroRNAs / Q000378:metabolism*; D018613:Microscopy, Confocal / Q000379:methods; D009369:Neoplasms / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D043244:Ribonuclease III / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C501467:RNH1 protein, human; D049452:Green Fluorescent Proteins; C517918:DROSHA protein, human; D043244:Ribonuclease III; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human