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

被引:21
|
作者
Zhang, Xiaomin [1 ]
Ameer, Fathima S. [1 ,2 ]
Azhar, Gohar [1 ,2 ]
Wei, Jeanne Y. [1 ]
机构
[1] Univ Arkansas Med Sci, Donald W Reynolds Dept Geriatr, Little Rock, AR 72205 USA
[2] Univ Arkansas Med Sci, Inst Aging, Little Rock, AR 72205 USA
关键词
novel isoforms; exon skipping and inclusion; age-related expression; mitochondrial function; NUCLEAR-LOCALIZATION; STRUCTURAL BASIS; SIR2; HOMOLOG; PREDICTION; PROTEINS; MITOCHONDRIAL; TRANSCRIPTION; EXPRESSION; REGULATOR; DATABASE;
D O I
10.3390/ijms22020473
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1 / 15
页数:15
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