Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1783640187242283008 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7824890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhangxiaomin alternativesplicingincreasessirtuingenefamilydiversityandmodulatestheirsubcellularlocalizationandfunction AT ameerfathimas alternativesplicingincreasessirtuingenefamilydiversityandmodulatestheirsubcellularlocalizationandfunction AT azhargohar alternativesplicingincreasessirtuingenefamilydiversityandmodulatestheirsubcellularlocalizationandfunction AT weijeanney alternativesplicingincreasessirtuingenefamilydiversityandmodulatestheirsubcellularlocalizationandfunction |