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Alternative Splicing Increases Sirtuin Gene Family Diversity and Modulates Their Subcellular Localization and Function

Alternative splicing generates multiple distinct isoforms that increase transcriptome and proteome diversity. There are seven sirtuin genes in humans, each consists of multiple exons that are likely to undergo alternative splicing. Our aim was to characterize the effect of alternative splicing on th...

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Detalles Bibliográficos
Autores principales: Zhang, Xiaomin, Ameer, Fathima S., Azhar, Gohar, Wei, Jeanne Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824890/
https://www.ncbi.nlm.nih.gov/pubmed/33418837
http://dx.doi.org/10.3390/ijms22020473
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author Zhang, Xiaomin
Ameer, Fathima S.
Azhar, Gohar
Wei, Jeanne Y.
author_facet Zhang, Xiaomin
Ameer, Fathima S.
Azhar, Gohar
Wei, Jeanne Y.
author_sort Zhang, Xiaomin
collection PubMed
description Alternative splicing generates multiple distinct isoforms that increase transcriptome and proteome diversity. There are seven sirtuin genes in humans, each consists of multiple exons that are likely to undergo alternative splicing. Our aim was to characterize the effect of alternative splicing on the sirtuin genes. Here, we report the identification of 23 human sirtuin isoforms, most of which were not previously reported. Five of the sirtuin genes had more than one isoform, whereas sirtuin-6 had nine isoforms. Exon skipping was the main event. Most of the sirtuin isoforms were deficient in parts of the protein domains, including the catalytic domain, the N- or C-terminus, nuclear localization signal or mitochondrial targeting signal. The domain loss caused potential structural changes. Three SIRT1 isoforms had a differential effect on the mitochondrial oxygen consumption rate. Age-related changes in the expression of SIRT1 isoforms were observed in the human heart in fetus, adults, and very old individuals. We also identified 15 sirtuin isoforms in mice. Our data indicate that alternative splicing increases sirtuin gene diversity and may modulate subcellular localization and function, thereby adding complexity to the gene regulation of mitochondrial respiration, metabolism, and cardiac function during maturation and aging.
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spelling pubmed-78248902021-01-24 Alternative Splicing Increases Sirtuin Gene Family Diversity and Modulates Their Subcellular Localization and Function Zhang, Xiaomin Ameer, Fathima S. Azhar, Gohar Wei, Jeanne Y. Int J Mol Sci Article Alternative splicing generates multiple distinct isoforms that increase transcriptome and proteome diversity. There are seven sirtuin genes in humans, each consists of multiple exons that are likely to undergo alternative splicing. Our aim was to characterize the effect of alternative splicing on the sirtuin genes. Here, we report the identification of 23 human sirtuin isoforms, most of which were not previously reported. Five of the sirtuin genes had more than one isoform, whereas sirtuin-6 had nine isoforms. Exon skipping was the main event. Most of the sirtuin isoforms were deficient in parts of the protein domains, including the catalytic domain, the N- or C-terminus, nuclear localization signal or mitochondrial targeting signal. The domain loss caused potential structural changes. Three SIRT1 isoforms had a differential effect on the mitochondrial oxygen consumption rate. Age-related changes in the expression of SIRT1 isoforms were observed in the human heart in fetus, adults, and very old individuals. We also identified 15 sirtuin isoforms in mice. Our data indicate that alternative splicing increases sirtuin gene diversity and may modulate subcellular localization and function, thereby adding complexity to the gene regulation of mitochondrial respiration, metabolism, and cardiac function during maturation and aging. MDPI 2021-01-06 /pmc/articles/PMC7824890/ /pubmed/33418837 http://dx.doi.org/10.3390/ijms22020473 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Xiaomin
Ameer, Fathima S.
Azhar, Gohar
Wei, Jeanne Y.
Alternative Splicing Increases Sirtuin Gene Family Diversity and Modulates Their Subcellular Localization and Function
title Alternative Splicing Increases Sirtuin Gene Family Diversity and Modulates Their Subcellular Localization and Function
title_full Alternative Splicing Increases Sirtuin Gene Family Diversity and Modulates Their Subcellular Localization and Function
title_fullStr Alternative Splicing Increases Sirtuin Gene Family Diversity and Modulates Their Subcellular Localization and Function
title_full_unstemmed Alternative Splicing Increases Sirtuin Gene Family Diversity and Modulates Their Subcellular Localization and Function
title_short Alternative Splicing Increases Sirtuin Gene Family Diversity and Modulates Their Subcellular Localization and Function
title_sort alternative splicing increases sirtuin gene family diversity and modulates their subcellular localization and function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824890/
https://www.ncbi.nlm.nih.gov/pubmed/33418837
http://dx.doi.org/10.3390/ijms22020473
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