Lassmann Timo, Maida Yoshiko, Tomaru Yasuhiro, Yasukawa Mami, Ando Yoshinari, Kojima Miki, Kasim Vivi, Simon Christophe, Daub Carsten O, Carninci Piero, Hayashizaki Yoshihide, Masutomi Kenkichi
RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
Cancer Stem Cell Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Int J Mol Sci. 2015 Jan 6;16(1):1192-208. doi: 10.3390/ijms16011192.
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).
微小RNA是一类抑制靶mRNA翻译的小非编码RNA。在人类中，大多数微小RNA由RNA聚合酶II转录成长链初级转录本，并分别通过两种核糖核酸酶III（DROSHA和DICER）的顺序切割加工成前体微小RNA和成熟微小RNA。尽管微小RNA在RNA沉默中的基本功能已逐渐被揭示，但对微小RNA表达调控机制的了解较少。在此，我们报告端粒酶逆转录酶（TERT）广泛影响成熟微小RNA的表达水平。基于深度测序的短RNA群体筛选显示，TERT的抑制导致THP-1细胞和HeLa细胞中表达的微小RNA下调。在TERT抑制下，初级和前体微小RNA水平也降低。抑制与TERT相互作用且在端粒之外发挥作用的蛋白质BRG1（也称为SMARCA4）或核干细胞因子，也获得了类似结果。这些结果表明，TERT可能通过非端粒酶机制在微小RNA生物合成的非常早期阶段对其进行调控。
