Dataset Information

The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription.

ABSTRACT: Small RNAs play a crucial role in genome defense against transposable elements and guide Argonaute proteins to nascent RNA transcripts to induce co-transcriptional gene silencing. However, the molecular basis of this process remains unknown. Here, we identify the conserved RNA helicase Aquarius/EMB-4 as a direct and essential link between small RNA pathways and the transcriptional machinery in Caenorhabditis elegans. Aquarius physically interacts with the germline Argonaute HRDE-1. Aquarius is required to initiate small-RNA-induced heritable gene silencing. HRDE-1 and Aquarius silence overlapping sets of genes and transposable elements. Surprisingly, removal of introns from a target gene abolishes the requirement for Aquarius, but not HRDE-1, for small RNA-dependent gene silencing. We conclude that Aquarius allows small RNA pathways to compete for access to nascent transcripts undergoing co-transcriptional splicing in order to detect and silence transposable elements. Thus, Aquarius and HRDE-1 act as gatekeepers coordinating gene expression and genome defense.

SUBMITTER: Akay A

PROVIDER: S-EPMC5554785 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription.

Akay Alper A Di Domenico Tomas T Suen Kin M KM Nabih Amena A Parada Guillermo E GE Larance Mark M Medhi Ragini R Berkyurek Ahmet C AC Zhang Xinlian X Wedeles Christopher J CJ Rudolph Konrad L M KLM Engelhardt Jan J Hemberg Martin M Ma Ping P Lamond Angus I AI Claycomb Julie M JM Miska Eric A EA

Developmental cell 20170801 3

Small RNAs play a crucial role in genome defense against transposable elements and guide Argonaute proteins to nascent RNA transcripts to induce co-transcriptional gene silencing. However, the molecular basis of this process remains unknown. Here, we identify the conserved RNA helicase Aquarius/EMB-4 as a direct and essential link between small RNA pathways and the transcriptional machinery in Caenorhabditis elegans. Aquarius physically interacts with the germline Argonaute HRDE-1. Aquarius is r ...[more]

PMID: 28787591

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Project description:Mammalian prion diseases are infectious neurodegenerative diseases caused by the self-templating form of the prion protein PrPSc. Much evidence supports the hypothesis that prions exist as a mixture of a dominant strain and minor prion strains. While it is known that prions can infect new species, the relative contribution of the dominant prion strain and minor strains in crossing the species barrier is unknown. We previously identified minor prion strains from a biologically cloned drowsy (DY) strain of hamster-adapted transmissible mink encephalopathy (TME). Here we show that these minor prion strains have increased infection efficiency to rabbit kidney epithelial cells that express hamster PrPC compared to the dominant strain DY TME. Using protein misfolding cyclic amplification (PMCA), we found that the dominant strain DY TME failed to convert mouse PrPC to PrPSc, even after several serial passages. In contrast, the minor prion strains isolated from biologically cloned DY TME robustly converted mouse PrPC to PrPSc in the first round of PMCA. This observation indicates that minor prion strains from the mutant spectra contribute to crossing the species barrier. Additionally, we found that the PMCA conversion efficiency for the minor prion strains tested was significantly different from each other and from the short-incubation period prion strain HY TME. This suggests that minor strain diversity may be greater than previously anticipated. These observations further expand our understanding of the mechanisms underlying the species barrier effect and has implications for assessing the zoonotic potential of prions.ImportancePrions from cattle with bovine spongiform encephalopathy have transmitted to humans, whereas scrapie from sheep and goats likely has not, suggesting that some prions can cross species barriers more easily than others. Prions are composed of a dominant strain and minor strains, and the contribution of each population to adapt to new replicative environments is unknown. Recently, minor prion strains were isolated from the biologically cloned prion strain DY TME, and these minor prion strains differed in properties from the dominant prion strain, DY TME. Here we found that these minor prion strains also differed in conversion efficiency and host range compared to the dominant strain DY TME. These novel findings provide evidence that minor prion strains contribute to interspecies transmission, underscoring the significance of minor strain components in important biological processes.

Dataset Information

The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription.

Publications

The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription.

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