Preferential retrotransposition in aging yeast mother cells is correlated with increased genome instability.
Preferential retrotransposition in aging yeast mother cells is correlated with increased genome instability.
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DOI：
10.1016/j.dnarep.2015.07.004
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发表时间：
2015-10
期刊：
影响因子：
3.8
通讯作者：
Maxwell PH
中科院分区：
文献类型：
--
作者：
Patterson MN;Scannapieco AE;Au PH;Dorsey S;Royer CA;Maxwell PH
在多种物种中，反转录转座子的表达或迁移率随着年龄的增长而增加，并可能在衰老过程中促进基因组的不稳定或基因表达的改变。然而，目前尚不清楚逆转座子在衰老过程中的激活是染色质和基因调控整体变化的间接结果，还是逆转座子特有机制的结果。通过对母细胞和子细胞的磁性细胞分选，发现酿酒酵母中一个显著的染色体Ty1反转录转座子在母细胞中相对于其子细胞的反向迁移率增加。老化母细胞的逆游走频率显著高于细胞年龄和年轻人群中的迁移率预测，从母细胞只有几代人老的时候开始。在老年母亲中，新的Ty1插入与总的染色体重排的相关性比在年轻细胞中更强，并且更多地发生在非首选的靶点。母细胞比子细胞更容易出现较高浓度的Ty1 Gag-GFP和明亮的病灶。在老年母细胞群体中，染色体外Ty1基因的水平也显著高于其子代细胞群体。这些观察结果与逆转录转座子特异的机制一致，该机制导致酵母母细胞在开始老化时优先发生逆转录转座，而不是通过与非常年老相关的表型变化激活。基于不同物种中逆转录转座子调控和后果的相似性，这些发现可能对理解许多生物体中的反转录转座子和衰老具有重要意义。
Retrotransposon expression or mobility is increased with age in multiple species and could promote genome instability or altered gene expression during aging. However, it is unclear whether activation of retrotransposons during aging is an indirect result of global changes in chromatin and gene regulation or a result of retrotransposon-specific mechanisms. Retromobility of a marked chromosomal Ty1 retrotransposon in Saccharomyces cerevisiae was elevated in mother cells relative to their daughter cells, as determined by magnetic cell sorting of mothers and daughters. Retromobility frequencies in aging mother cells were significantly higher than those predicted by cell age and the rate of mobility in young populations, beginning when mother cells were only several generations old. New Ty1 insertions in aging mothers were more strongly correlated with gross chromosome rearrangements than in young cells and were more often at non-preferred target sites. Mother cells were more likely to have high concentrations and bright foci of Ty1 Gag-GFP than their daughter cells. Levels of extrachromosomal Ty1 cDNA were also significantly higher in aged mother cell populations than their daughter cell populations. These observations are consistent with a retrotransposon-specific mechanism that causes retrotransposition to occur preferentially in yeast mother cells as they begin to age, as opposed to activation by phenotypic changes associated with very old age. These findings will likely be relevant for understanding retrotransposons and aging in many organisms, based on similarities in regulation and consequences of retrotransposition in diverse species.