Cardiac RNase Z edited via CRISPR-Cas9 drives heart hypertrophy in Drosophila
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 th...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212119/?tool=EBI |
| _version_ | 1827940224390397952 |
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| author | Ekaterina Migunova Saathvika Rajamani Stefania Bonanni Fei Wang Chao Zhou Edward B. Dubrovsky |
| author_facet | Ekaterina Migunova Saathvika Rajamani Stefania Bonanni Fei Wang Chao Zhou Edward B. Dubrovsky |
| author_sort | Ekaterina Migunova |
| collection | DOAJ |
| description | 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’-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 Drosophila models that carry cardiomyopathy-linked alleles of RNase Z 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 RNase Z linked CM is driven by cell autonomous mechanisms. |
| first_indexed | 2024-03-13T09:06:03Z |
| format | Article |
| id | doaj.art-95263ed638e748ac813b900bdd3d5400 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-13T09:06:03Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-95263ed638e748ac813b900bdd3d54002023-05-28T05:31:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01185Cardiac RNase Z edited via CRISPR-Cas9 drives heart hypertrophy in DrosophilaEkaterina MigunovaSaathvika RajamaniStefania BonanniFei WangChao ZhouEdward B. DubrovskyCardiomyopathy (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’-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 Drosophila models that carry cardiomyopathy-linked alleles of RNase Z 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 RNase Z linked CM is driven by cell autonomous mechanisms.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212119/?tool=EBI |
| spellingShingle | Ekaterina Migunova Saathvika Rajamani Stefania Bonanni Fei Wang Chao Zhou Edward B. Dubrovsky Cardiac RNase Z edited via CRISPR-Cas9 drives heart hypertrophy in Drosophila PLoS ONE |
| title | Cardiac RNase Z edited via CRISPR-Cas9 drives heart hypertrophy in Drosophila |
| title_full | Cardiac RNase Z edited via CRISPR-Cas9 drives heart hypertrophy in Drosophila |
| title_fullStr | Cardiac RNase Z edited via CRISPR-Cas9 drives heart hypertrophy in Drosophila |
| title_full_unstemmed | Cardiac RNase Z edited via CRISPR-Cas9 drives heart hypertrophy in Drosophila |
| title_short | Cardiac RNase Z edited via CRISPR-Cas9 drives heart hypertrophy in Drosophila |
| title_sort | cardiac rnase z edited via crispr cas9 drives heart hypertrophy in drosophila |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212119/?tool=EBI |
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