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Highly efficacious antiviral protection of plants by small interfering RNAs identified in vitro.

ABSTRACT: In response to a viral infection, the plant's RNA silencing machinery processes viral RNAs into a huge number of small interfering RNAs (siRNAs). However, a very few of these siRNAs actually interfere with viral replication. A reliable approach to identify these immunologically effective siRNAs (esiRNAs) and to define the characteristics underlying their activity has not been available so far. Here, we develop a novel screening approach that enables a rapid functional identification of antiviral esiRNAs. Tests on the efficacy of such identified esiRNAs of a model virus achieved a virtual full protection of plants against a massive subsequent infection in transient applications. We find that the functionality of esiRNAs depends crucially on two properties: the binding affinity to Argonaute proteins and the ability to access the target RNA. The ability to rapidly identify functional esiRNAs could be of great benefit for all RNA silencing-based plant protection measures against viruses and other pathogens.

SUBMITTER: Gago-Zachert S

PROVIDER: S-EPMC6755098 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Highly efficacious antiviral protection of plants by small interfering RNAs identified in vitro.

Gago-Zachert Selma S Schuck Jana J Weinholdt Claus C Knoblich Marie M Pantaleo Vitantonio V Grosse Ivo I Gursinsky Torsten T Behrens Sven-Erik SE

Nucleic acids research 20190901 17

In response to a viral infection, the plant's RNA silencing machinery processes viral RNAs into a huge number of small interfering RNAs (siRNAs). However, a very few of these siRNAs actually interfere with viral replication. A reliable approach to identify these immunologically effective siRNAs (esiRNAs) and to define the characteristics underlying their activity has not been available so far. Here, we develop a novel screening approach that enables a rapid functional identification of antiviral ...[more]

PMID: 31433052

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Project description:BackgroundThe discovery of RNA interference phenomenon (RNAi) and understanding of its mechanisms has revolutionized our views on many molecular processes in the living cell. Among the other, RNAi is involved in silencing of transposable elements and in inhibition of virus infection in various eukaryotic organisms. Recent experimental studies demonstrate few cases of viral replication suppression via complementary interactions between the mammalian small RNAs and viral transcripts.Presentation of the hypothesisIt was found that >50% of the human genome is transcribed in different cell types and that these transcripts are mainly not associated with known protein coding genes, but represent non-coding RNAs of unknown functions. We propose a hypothesis that mammalian DNAs encode thousands RNA motifs that may serve for antiviral protection. We also presume that the evolutional success of some groups of genomic repeats and, in particular, of transposable elements (TEs) may be due to their ability to provide antiviral RNA motifs to the host organism. Intense genomic repeat propagation into the genome would inevitably cause bidirectional transcription of these sequences, and the resulting double-stranded RNAs may be recognized and processed by the RNA interference enzymatic machinery. Provided that these processed target motifs may be complementary to viral transcripts, fixation of the repeats into the host genome may be of a considerable benefit to the host. It fits with our bioinformatical data revealing thousands of 21-28 bp long motifs identical between human DNA and human-pathogenic adenoviral and herpesviral genomes. Many of these motifs are transcribed in human cells, and the transcribed part grows proportionally to their lengths. Many such motifs are included in human TEs. For example, one 23 nt-long motif that is a part of human abundant Alu retrotransposon, shares sequence identity with eight human adenoviral genomes.Testing the hypothesisThis hypothesis could be tested on various mammalian species and viruses infecting mammalian cells.Implications of the hypothesisThis hypothesis proposes that mammalian organisms may use their own genomes as sources of thousands of putative interfering RNA motifs that can be recruited to repress intracellular pathogens like proliferating viruses.ReviewersThis article was reviewed by Eugene V. Koonin, Valerian V. Dolja and Yuri V. Shpakovski.

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Highly efficacious antiviral protection of plants by small interfering RNAs identified in vitro.

Publications

Highly efficacious antiviral protection of plants by small interfering RNAs identified in vitro.

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