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. 2019 Nov 18;25(2):308–320. doi: 10.1038/s41380-019-0597-8

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a First RNA polymerase II transcribes the miRNA gene resulting in a pri-miRNA with a hairpin loop structure. This structure is cleaved by DROSHA and DGCR8 (blue arrows) into a pre-miRNA and transported out of the cell by EXPO-5. Dicer and TRBP cleave away the loop structure (gray arrows) leaving a miRNA-miRNA* duplex. AGO 2 loads the mature miRNA (red), forming the RISC complex, and the miRNA* strand (black) is degraded. RISC can bind to specific gene targets and lead to translational repression. b Methylation at the miRNA gene promoter region can reduce transcription of pri-miRNAs by RNA Pol II. This results in decreased production of mature miRNAs and altered downstream repression of their target genes. c In the presence of compatible circRNAs, there is competition for miRNA binding. Each circRNA can have multiple binding sites for a single miRNA effectively reducing miRNA-target gene interactions and their associated translational repression. As a result, both methylation and circRNAs can promote protein production. Abbreviations: miRNA (microRNA), RNA Pol II (RNA Polymerase II), pri-miRNA (primary miRNA), pre-miRNA (precursor miRNA), EXPO-5 (exportin-5), TRBP (Tar RNA-binding protein), RISC (RNA-induced silencing complex), AGO 2 (argonaute), tRNA (transfer RNA), CH₃ (methyl group), mRNA (messenger RNA), circRNA (circular RNA)