Organ-, sex- and age-dependent patterns of endogenous L1 mRNA expression at a single locus resolution.

Organ-, sex- and age-dependent patterns of endogenous L1 mRNA expression at a single locus resolution.
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DOI:
10.1093/nar/gkab369
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发表时间:
2021-06-04
影响因子:
14.9
通讯作者:
Belancio VP
Belancio VP
中科院分区:
生物学2区
文献类型:
--
作者:
Stow EC;Kaul T;deHaro DL;Dem MR;Beletsky AG;Morales ME;Du Q;LaRosa AJ;Yang H;Smither E;Baddoo M;Ungerleider N;Deininger P;Belancio VP

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L1 mRNA的表达是L1复制粘贴扩增循环的第一步,是L1相关基因组不稳定性的先决条件。我们使用了严格的生物信息学方法来解析L1 mRNA转录本,并以位点特异性分辨率测量小鼠和大鼠器官中L1 mRNA的表达水平。该分析确定啮齿动物中L1基因座的mRNA表达表现出显著的器官特异性,同一生物体的器官之间共享的基因座不到0.8%。L1 mRNA表达的这种器官特异性在雄性和雌性小鼠中以及在各年龄组中得以保留。我们发现性别之间的L1 mRNA表达存在显着差异,雄性和雌性小鼠之间只有5%的表达L1位点。此外,我们报告的总L1 mRNA的表达水平和表达的L1位点的数量和频谱随年龄波动作为自变量,表现出不同的模式,在不同的器官和性别。总体而言,我们在器官和性别之间以及在2至22个月的年龄范围内进行的比较建立了以前无法预见的体内L1 mRNA表达的动态变化。这些研究结果建立了一个广泛的生物变量,将指导未来的研究内源性L1 mRNA表达图谱的开始。
Expression of L1 mRNA, the first step in the L1 copy-and-paste amplification cycle, is a prerequisite for L1-associated genomic instability. We used a reported stringent bioinformatics method to parse L1 mRNA transcripts and measure the level of L1 mRNA expressed in mouse and rat organs at a locus-specific resolution. This analysis determined that mRNA expression of L1 loci in rodents exhibits striking organ specificity with less than 0.8% of loci shared between organs of the same organism. This organ specificity in L1 mRNA expression is preserved in male and female mice and across age groups. We discovered notable differences in L1 mRNA expression between sexes with only 5% of expressed L1 loci shared between male and female mice. Moreover, we report that the levels of total L1 mRNA expression and the number and spectrum of expressed L1 loci fluctuate with age as independent variables, demonstrating different patterns in different organs and sexes. Overall, our comparisons between organs and sexes and across ages ranging from 2 to 22 months establish previously unforeseen dynamic changes in L1 mRNA expression in vivo. These findings establish the beginning of an atlas of endogenous L1 mRNA expression across a broad range of biological variables that will guide future studies.
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