{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:57:20Z","timestamp":1753869440097,"version":"3.41.2"},"reference-count":40,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Adenovirus expresses two non\u2010coding virus\u2010associated (VA) RNAs: VA I RNA and VA II RNA. Adenovirus\u2010expressed VA RNAs interfere with the microRNA (miRNA) pathway by competing with precursor miRNAs. The processing pattern of primary miRNA (pri\u2010miRNA) and factors to affect its processing are not exactly known when using adenovirus for the delivery of pri\u2010miRNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To observe pri\u2010miRNA processing, plasmid construct encoding pri\u2010miRNA was co\u2010transfected with VA I\/II RNA expression plasmid, or recombinant adenovirus encoding pri\u2010miRNA was generated and infected. Levels of miRNAs, VA I RNA and VA II RNA were analyzed by a quantitative real\u2010time PCR (RT\u2010PCR). VA I\u2013II full\u2010length RNA was analyzed by a RT\u2010PCR. RNA immunoprecipitation analysis to pull\u2010down the VA I\u2013II full\u2010length RNA binding with Drosha was conducted with Drosha antibody.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>pri\u2010miRNA was normally processed into mature miRNA when it was expressed in cells using plasmid. However, miRNA maturation was impaired when pri\u2010miRNA was delivered and expressed using adenovirus. Of note, pri\u2010miRNA processing was observed to be blocked by VA RNA expression. Such blocked processing could be recovered by introducing antisense RNA of VA RNA, anti\u20103\u2032VA RNA. In addition, VA RNAs were transcribed into VA I\u2013II full\u2010length RNA, which was found to bind and sequester Drosha.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Adenovirus infection downregulated the processing of pri\u2010miRNAs in cells, and such downregulation could be derived from VA I\u2013II full\u2010length RNAs in pri\u2010miRNA\u2010like form through competitively binding to Drosha protein. These results indicated that the expression of adenovirus VA RNAs should be inhibited for successful delivery and expression of pri\u2010miRNA or shRNA in cells using adenovirus.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3564","type":"journal-article","created":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T05:33:18Z","timestamp":1689139998000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adenovirus VA RNAs impair maturation of primary microRNA"],"prefix":"10.1002","volume":"25","author":[{"given":"Ji Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"R&amp;D Center Rznomics Inc.  Seongnam Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioconvergence Engineering, Research Institute of Advanced Omics Dankook University  Yongin Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong\u2010Wook","family":"Lee","sequence":"additional","affiliation":[{"name":"R&amp;D Center Rznomics Inc.  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