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).
Highlights
MicroRNAs are small non-coding RNAs that control diverse physiological and pathological processes through post-transcriptional regulation of protein synthesis
Screening of Short RNAs Regulated by Telomerase Reverse Transcriptase (TERT)
We observed a high amount of transfer RNA fragments in all short RNA samples (Figures S2–S4), which is common when sequencing RNAs longer than 30 nucleotides [22]
Summary
MicroRNAs (miRNAs) are small non-coding RNAs that control diverse physiological and pathological processes through post-transcriptional regulation of protein synthesis. The basic steps in miRNA biogenesis are well understood [1]. Primary miRNA transcripts are cleaved by DROSHA, and the cleaved products are exported from the nucleus by XPO5 and, cleaved by DICER. In addition to the canonical proteins, a number of post-transcriptional regulators of miRNA biogenesis have been discovered [2]. Somewhat less is known about the transcriptional regulation of miRNAs themselves. Most of primary miRNAs (pri-miRNAs) are transcribed in an RNA polymerase II (Pol II)-dependent manner, and recent promoter analyses suggest transcriptional regulation of miRNAs might be similar to that of protein-coding genes.
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