A novel role of TRIM28 B box domain in L1 retrotransposition and ORF2p-mediated cDNA synthesis.
A novel role of TRIM28 B box domain in L1 retrotransposition and ORF2p-mediated cDNA synthesis.
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DOI：
10.1093/nar/gkad247
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发表时间：
2023-05-22
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
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长散布元件1（LINE-1或L1）整合通过各种机制受到许多细胞因子的影响。这些因素中的一些是L1扩增所需的，而另一些则抑制或增强L1传播过程中的特定步骤。先前，TRIM 28已被鉴定为通过其在染色质重塑中的典型作用抑制转座因子，包括L1表达。在这里，我们报告，TRIM 28通过其B框结构域增加L1反转录转座，并促进培养细胞中较短的cDNA和L1插入物的产生。与后者相一致，我们观察到TRIM 28 mRNA表达较高的子宫内膜、卵巢和前列腺肿瘤中肿瘤特异性L1插入短于TRIM 28表达较低的肿瘤。我们确定，在B盒结构域中的三个氨基酸参与TRIM 28多聚化是关键的L1反转录转座和cDNA合成的影响。我们提供的证据表明，B盒的其他两个成员在VI类TRIM蛋白，TRIM 24和TRIM 33，也增加L1反转录转座。我们的研究结果可能会导致更好地了解宿主/L1进化军备竞赛的生殖细胞和它们在肿瘤发生过程中的相互作用。
The long interspersed element 1 (LINE-1 or L1) integration is affected by many cellular factors through various mechanisms. Some of these factors are required for L1 amplification, while others either suppress or enhance specific steps during L1 propagation. Previously, TRIM28 has been identified to suppress transposable elements, including L1 expression via its canonical role in chromatin remodeling. Here, we report that TRIM28 through its B box domain increases L1 retrotransposition and facilitates shorter cDNA and L1 insert generation in cultured cells. Consistent with the latter, we observe that tumor specific L1 inserts are shorter in endometrial, ovarian, and prostate tumors with higher TRIM28 mRNA expression than in those with lower TRIM28 expression. We determine that three amino acids in the B box domain that are involved in TRIM28 multimerization are critical for its effect on both L1 retrotransposition and cDNA synthesis. We provide evidence that B boxes from the other two members in the Class VI TRIM proteins, TRIM24 and TRIM33, also increase L1 retrotransposition. Our findings could lead to a better understanding of the host/L1 evolutionary arms race in the germline and their interplay during tumorigenesis.
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DOI：
10.1146/annurev-genom-082509-141802
发表时间：
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影响因子：
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