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Rather, a number of DNA viruses, including herpesviruses, utilize post-transcriptional silencing systems for their survival. Here we show that Dicer efficiently suppresses the replication of adenovirus (Ad) <jats:italic>via<\/jats:italic> cleavage of Ad-encoding small RNAs (VA-RNAs), which efficiently promote Ad replication <jats:italic>via<\/jats:italic> the inhibition of eIF2\u03b1 phosphorylation, to viral microRNAs (mivaRNAs). The Dicer knockdown significantly increases the copy numbers of VA-RNAs, leading to the efficient inhibition of eIF2\u03b1 phosphorylation and the subsequent promotion of Ad replication. Conversely, overexpression of Dicer significantly inhibits Ad replication. Transfection with mivaRNA does not affect eIF2\u03b1 phosphorylation or Ad replication. These results indicate that Dicer-mediated processing of VA-RNAs leads to loss of activity of VA-RNAs for enhancement of Ad replication and that Dicer functions as a defence system against Ad in mammalian cells.<\/jats:p>","DOI":"10.1038\/srep27598","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T09:32:45Z","timestamp":1465291965000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA"],"prefix":"10.1038","volume":"6","author":[{"given":"Mitsuhiro","family":"Machitani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuminori","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisaku","family":"Wakabayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Tomita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Tachibana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Mizuguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,6,7]]},"reference":[{"key":"BFsrep27598_CR1","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1101\/gad.1793309","volume":"23","author":"JL Umbach","year":"2009","unstructured":"Umbach, J. 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