RNA interference: more than a research tool in the vertebrates' adaptive immunity - PubMed (original) (raw)

RNA interference: more than a research tool in the vertebrates' adaptive immunity

Johnson Mak. Retrovirology. 2005.

Abstract

In recent years, RNA silencing, usage of small double stranded RNAs of approximately 21 - 25 base pairs to regulate gene expression, has emerged as a powerful research tool to dissect the role of unknown host cell factors in this 'post-genomic' era. While the molecular mechanism of RNA silencing has not been precisely defined, the revelation that small RNA molecules are equipped with this regulatory function has transformed our thinking on the role of RNA in many facets of biology, illustrating the complexity and the dynamic interplay of cellular regulation. As plants and invertebrates lack the protein-based adaptive immunity that are found in jawed vertebrates, the ability of RNA silencing to shut down gene expression in a sequence-specific manner offers an explanation of how these organisms counteract pathogen invasions into host cells. It has been proposed that this type of RNA-mediated defence mechanism is an ancient form of immunity to offset the transgene-, transposon- and virus-mediated attack. However, whether 1) RNA silencing is a natural immune response in vertebrates to suppress pathogen invasion; or 2) vertebrate cells have evolved to counteract invasion in a 'RNA silencing' independent manner remains to be determined. A number of recent reports have provided tantalizing clues to support the view that RNA silencing functions as a physiological response to regulate viral infection in vertebrate cells. Amongst these, two manuscripts that are published in recent issues of Science and Immunity, respectively, have provided some of the first direct evidences that RNA silencing is an important component of antiviral defence in vertebrate cells. In addition to demonstrating RNA silencing to be critical to vertebrate innate immunity, these studies also highlight the potential of utilising virus-infection systems as models to refine our understanding on the molecular determinants of RNA silencing in vertebrate cells.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Model of RNA silencing pathway. The biogenesis of RNA silencing transcripts can be derived from either the host cell nucleus mRNA pathway to yield miRNA or the cytoplasmic double strand RNA to yield siRNA. HIV-1 and PFV have evolved to use their transcriptional factor to counteract this ancient host cell immunity.

Similar articles

Cited by

References

    1. Napoli C, Lemieux C, Jorgensen R. Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans. Plant Cell. 1990;2:279–289. doi: 10.1105/tpc.2.4.279. - DOI - PMC - PubMed
    1. van der Krol AR, Mur LA, Beld M, Mol JN, Stuitje AR. Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression. Plant Cell. 1990;2:291–299. doi: 10.1105/tpc.2.4.291. - DOI - PMC - PubMed
    1. Lindbo JA, Dougherty WG. Untranslatable transcripts of the tobacco etch virus coat protein gene sequence can interfere with tobacco etch virus replication in transgenic plants and protoplasts. Virology. 1992;189:725–733. doi: 10.1016/0042-6822(92)90595-G. - DOI - PubMed
    1. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998;391:806–811. doi: 10.1038/35888. - DOI - PubMed
    1. Cogoni C, Irelan JT, Schumacher M, Schmidhauser TJ, Selker EU, Macino G. Transgene silencing of the al-1 gene in vegetative cells of Neurospora is mediated by a cytoplasmic effector and does not depend on DNA-DNA interactions or DNA methylation. Embo J. 1996;15:3153–3163. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources