title: Telomerase reverse transcriptase regulates microRNAs.
abstract: MicroRNAs are small non-coding RNAs that inhibit the translation of target mRNAs. In humans, most microRNAs are transcribed by RNA polymerase II as long primary transcripts and processed by sequential cleavage of the two RNase III enzymes, DROSHA and DICER, into precursor and mature microRNAs, respectively. Although the fundamental functions of microRNAs in RNA silencing have been gradually uncovered, less is known about the regulatory mechanisms of microRNA expression. Here, we report that telomerase reverse transcriptase (TERT) extensively affects the expression levels of mature microRNAs. Deep sequencing-based screens of short RNA populations revealed that the suppression of TERT resulted in the downregulation of microRNAs expressed in THP-1 cells and HeLa cells. Primary and precursor microRNA levels were also reduced under the suppression of TERT. Similar results were obtained with the suppression of either BRG1 (also called SMARCA4) or nucleostemin, which are proteins interacting with TERT and functioning beyond telomeres. These results suggest that TERT regulates microRNAs at the very early phases in their biogenesis, presumably through non-telomerase mechanism(s).
authors.affiliation: RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. lassmann@gsc.riken.jp.
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.affiliation: Cancer Stem Cell Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. ymaida@ncc.go.jp.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Maida
authors.affiliation: RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. tomaru@gsc.riken.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tomaru
authors.affiliation: Cancer Stem Cell Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. myasukaw@ncc.go.jp.
authors.forename: Mami
authors.initials: M
authors.lastname: Yasukawa
authors.affiliation: RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. yando@gsc.riken.jp.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Ando
authors.affiliation: RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. miki1978@gsc.riken.jp.
authors.forename: Miki
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Cancer Stem Cell Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. vkasim@ncc.go.jp.
authors.forename: Vivi
authors.initials: V
authors.lastname: Kasim
authors.affiliation: RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. simon@gsc.riken.jp.
authors.forename: Christophe
authors.initials: C
authors.lastname: Simon
authors.affiliation: RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. daub@gsc.riken.jp.
authors.forename: Carsten O
authors.initials: CO
authors.lastname: Daub
authors.affiliation: RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. carninci@riken.jp.
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.affiliation: RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.affiliation: Cancer Stem Cell Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. kmasutom@ncc.go.jp.
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Masutomi
mesh_terms: D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C469949:GNL3 protein, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D019098:Telomerase; C408087:DICER1 protein, human; D043244:Ribonuclease III; D019204:GTP-Binding Proteins; C084108:SMARCA4 protein, human; D004265:DNA Helicases; D053487:DEAD-box RNA Helicases