RNA virus-encoded microRNAs: biogenesis, functions and perspectives on application

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Zhan et al. ExRNA (2020) 2:15 https://doi.org/10.1186/s41544-020-00056-z

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RNA virus-encoded microRNAs: biogenesis, functions and perspectives on application Shoubin Zhan, Yanbo Wang and Xi Chen*

Abstract MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression at the posttranscriptional level and play a crucial role in development and many diseases. The discovery of miRNAs has greatly expanded our understanding of the intricate scenario of genome-wide regulation. Over the last two decades, hundreds of virusencoded miRNAs have been identified, most of which are from DNA viruses. Although the number of reported RNA virus-derived miRNAs is increasing, current knowledge of their roles in physiological and pathological processes has remained lacking. In this review, we discuss the biogenesis and biological functions of RNA virusencoded miRNAs and their proposed roles in virus-host interactions and further underscore their potential value in the diagnosis and treatment of viral diseases. Keywords: RNA virus, miRNA, Biogenesis, Biological function

Background Discovery, biogenesis and functions of miRNAs

MicroRNAs (miRNAs) are a class of small, singlestranded noncoding RNAs of approximately 22 nucleotides (nt) in length that can regulate the expression of a target gene at the posttranscriptional level [1–3]. Since the discovery of the first miRNA, lin-4, 27 years ago [4], numerous miRNAs have been identified in animals, plants and viruses [5, 6] and found to play important roles in development and disease. Canonical miRNAs are mainly transcribed by RNA polymerase II (Pol II) to generate the primary miRNA transcripts (pri-miRNAs) from either the protein-coding region or the noncoding region of the genome [7]. PrimiRNAs are usually more than one kilobase long with stem-loop structures inside [8]. Pri-miRNA can be cleaved by the nuclear RNaseIII Drosha to generate ~ 60–70 nt precursor miRNA (pre-miRNA) hairpin followed by export to the cytoplasm where RNaseIII * Correspondence: [email protected] Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology and Department of Physiology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China

Dicer further processes pre-miRNAs into ~ 22 nt double-stranded RNAs [9]. The guide strand (mature miRNA) of the miRNA duplexes is then loaded into the RNA-induced silencing complex (RISC), whereas the other strand is degraded [10, 11]. The miRNA-loaded RISCs (miRISCs) bind the 3′ untranslated region (3′ UTR) of mRNAs and direct target transcripts repression [12]. As miRNAs and their targets are not paired one to one, a single miRNA can target multiple sites of transcripts and a single gene can be targeted by several miRNAs; miRNAs and their targets are involved in a complex regulatory network [6, 13]. Virus-host interaction and mic