{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T22:01:09Z","timestamp":1763071269729,"version":"3.40.5"},"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of health","award":["R01-EB025209"],"award-info":[{"award-number":["R01-EB025209"]}]},{"name":"National Institute of Health","award":["R01-HL156265"],"award-info":[{"award-number":["R01-HL156265"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cardiomyopathy (CM) is a group of diseases distinguished by morphological and functional abnormalities in the myocardium. It is etiologically heterogeneous and may develop via cell autonomous and\/or non-autonomous mechanisms. One of the most severe forms of CM has been linked to the deficiency of the ubiquitously expressed RNase Z endoribonuclease. RNase Z cleaves off the 3\u2019-trailer of both nuclear and mitochondrial primary tRNA (pre-tRNA) transcripts. Cells mutant for RNase Z accumulate unprocessed pre-tRNA molecules. Patients carrying RNase Z variants with reduced enzymatic activity display a plethora of symptoms including muscular hypotonia, microcephaly and severe heart hypertrophy; still, they die primarily due to acute heart decompensation. Determining whether the underlying mechanism of heart malfunction is cell autonomous or not will provide an opportunity to develop novel strategies of more efficient treatments for these patients. In this study, we used CRISPR-TRiM technology to create <jats:italic>Drosophila<\/jats:italic> models that carry cardiomyopathy-linked alleles of <jats:italic>RNase Z<\/jats:italic> only in the cardiomyocytes. We found that this modification is sufficient for flies to develop heart hypertrophy and systolic dysfunction. These observations support the idea that the <jats:italic>RNase Z<\/jats:italic> linked CM is driven by cell autonomous mechanisms.<\/jats:p>","DOI":"10.1371\/journal.pone.0286214","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T17:31:45Z","timestamp":1685035905000},"page":"e0286214","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cardiac RNase Z edited via CRISPR-Cas9 drives heart hypertrophy in Drosophila"],"prefix":"10.1371","volume":"18","author":[{"given":"Ekaterina","family":"Migunova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saathvika","family":"Rajamani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Bonanni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0640-5538","authenticated-orcid":true,"given":"Edward B.","family":"Dubrovsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"pone.0286214.ref001","first-page":"785","article-title":"Prevalence of hypertrophic cardiomyopathy in a general population of young adults. 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