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Int. J. Mol. Sci. 2015, 16(1), 1192-1208; doi:10.3390/ijms16011192

Telomerase Reverse Transcriptase Regulates microRNAs

1
RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan
2
Cancer Stem Cell Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
3
Precursory Research for Embryonic Science and Technology (PREST), Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Martin Pichler
Received: 22 November 2014 / Accepted: 26 December 2014 / Published: 6 January 2015
(This article belongs to the Collection Regulation by Non-Coding RNAs)
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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). View Full-Text
Keywords: telomerase reverse transcriptase; microRNA; RNA-dependent RNA polymerase; cancer telomerase reverse transcriptase; microRNA; RNA-dependent RNA polymerase; cancer
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MDPI and ACS Style

Lassmann, T.; Maida, Y.; Tomaru, Y.; Yasukawa, M.; Ando, Y.; Kojima, M.; Kasim, V.; Simon, C.; Daub, C.O.; Carninci, P.; Hayashizaki, Y.; Masutomi, K. Telomerase Reverse Transcriptase Regulates microRNAs. Int. J. Mol. Sci. 2015, 16, 1192-1208.

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