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Transcriptional dysregulation is one of the main cellular processes affected by mutant Huntingtin (mHtt). In this study, we investigate the alterations in miRNA and mRNA expression levels in a Drosophila model of HD by RNA sequencing and assess the functional effects of misregulated miRNAs in vivo. We found that in head samples of HD flies, the level of 32 miRNAs changed significantly; half of these were upregulated, while the other half were downregulated. After comparing miRNA and mRNA expression data, we discovered similarities in the impacted molecular pathways. Additionally, we observed that the putative targets of almost all dysregulated miRNAs were overrepresented among the upregulated mRNAs. We tested the effects of overexpression of five misregulated miRNAs in the HD model and found that while mir-10 and mir-219 enhanced, mir-137, mir-305, and mir-1010 ameliorated mHtt-induced phenotypes. Based on our results, we propose that while altered expression of mir-10, mir-137, and mir-1010 might be part of HD pathology, the upregulation of mir-305 might serve as a compensatory mechanism as a response to mHtt-induced transcriptional dysregulation.<\/jats:p>","DOI":"10.3390\/ijms241511942","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T01:27:46Z","timestamp":1690421266000},"page":"11942","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Dysregulated miRNA and mRNA Expression Affect Overlapping Pathways in a Huntington\u2019s Disease Model"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6189-3100","authenticated-orcid":false,"given":"N\u00f3ra","family":"Zsindely","sequence":"first","affiliation":[{"name":"Department of Genetics, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5464-1135","authenticated-orcid":false,"given":"G\u00e1bor","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fruzsina","family":"Si\u00e1gi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary"},{"name":"Doctoral School in Biology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Farkas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary"},{"name":"Doctoral School in Biology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8411-626X","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Bodai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington Disease","volume":"1","author":"Bates","year":"2015","journal-title":"Nat. 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