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. 2012 Jun 26:10:58.
doi: 10.1186/1741-7007-10-58.

RNAi in the regulation of mammalian viral infections

Kuan-Teh Jeang  1
Affiliations

RNAi in the regulation of mammalian viral infections

Kuan-Teh Jeang. BMC Biol. .

Abstract

Although RNA interference (RNAi) is known to play an important part in defense against viruses of invertebrates, its contribution to mammalian anti-viral defense has been a matter of dispute. This is surprising because all components of the RNAi machinery necessary for robust RNAi-mediated restriction of viruses are conserved in mammals, and the introduction of synthetic small interfering RNAs (siRNAs) into cells efficiently silences the replication of viruses that contain siRNA complementary sequences in those cells. Here, I discuss the reasons for the dispute, and review the evidence that RNAi is a part of the physiological defense of mammalian cells against viral infections.

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Figures

Figure 1
Figure 1
miRNA-, siRNA-, piRNA-RISC complexes effect complementarity-driven silencing of targeted mRNAs. Small miRNAs, siRNAs, or piRNAs (red) serve as guide sequences within the RNA-induced silencing complex (RISC) to capture target mRNA via incomplete (miRNA) or complete (siRNA, piRNA) base-pairing. The expression of the targeted mRNA is silenced either by RNA degradation or by inhibition of translation.
Figure 2
Figure 2
Several ways that RNAi can regulate viruses in mammalian cells. Left: cell-endogenous endo-miRNAs are engaged in RISC complexes to target partially homologous viral transcripts. Middle: virus-encoded miRNA can be processed as exo-miRNAs that are engaged with RISC for interaction with other viral RNAs. Right: viruses that contain shRNA sequences (for example, lentiviral shRNA libraries) are processed into exo-siRNAs. The double-stranded RNAs (hairpins) are processed in the RISC into single-stranded guide RNAs that bind to complementary sequences in the mRNA, thus recruiting RISC, which degrades the mRNA or inhibits its translation. Transposable elements and endogenous retroviruses produce endo-siRNAs in mammalian cells. Both exo-siRNAs and endo-siRNAs can be incorporated into RISC complexes in mammalian cells to silence homologous target RNAs. Multiple transcripts (blue) are indicative of differently spliced RNAs.
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