Abstract
RNA silencing is a posttranscriptional gene silencing mechanism directed by endogenous small non-coding RNAs called microRNAs (miRNAs). By contrast, the type-I interferon (IFN) response is an innate immune response induced by exogenous RNAs, such as viral RNAs. Endogenous and exogenous RNAs have typical structural features and are recognized accurately by specific RNA-binding proteins in each pathway. In mammalian cells, both RNA silencing and the IFN response are induced by double-stranded RNAs (dsRNAs) in the cytoplasm, but have long been considered two independent pathways. However, recent reports have shed light on crosstalk between the two pathways, which are mutually regulated by protein–protein interactions triggered by viral infection. This review provides brief overviews of RNA silencing and the IFN response and an outline of the molecular mechanism of their crosstalk and its biological implications. Crosstalk between RNA silencing and the IFN response may reveal a novel antiviral defense system that is regulated by miRNAs in mammalian cells.
Highlights
RNA silencing is a posttranscriptional gene silencing mechanism that is conserved among diverse organisms and is induced by microRNA, an approximately 22-nucleotide long endogenous non-coding double-stranded RNA [1]
This specificity may be the reason that RNA silencing and the IFN response have been considered two independent pathways, despite both being induced by double-stranded RNAs (dsRNAs) in the cytoplasm
Recent reports, including ours, have provided a novel perspective that RNA silencing and the IFN response are mutually regulated through protein–protein interactions triggered by RNA virus infection [26,27,28,29,30,31,32,33]
Summary
RNA silencing is a posttranscriptional gene silencing mechanism that is conserved among diverse organisms and is induced by microRNA (miRNA), an approximately 22-nucleotide (nt) long endogenous non-coding double-stranded RNA (dsRNA) [1]. Endogenous or exogenous RNAs with typical structural characteristics are accurately recognized by specific types of RNA-binding proteins acting in one of the two pathways [6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25] This specificity may be the reason that RNA silencing and the IFN response have been considered two independent pathways, despite both being induced by dsRNAs in the cytoplasm. Crosstalk between RNA silencing and the IFN response is a conserved mechanism specific to mammalian cells that might reveal an unresolved molecular mechanism of antiviral defense in mammalian cells
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