通过tRNA衍生小RNA进行LTR-逆转移子控制
Andrea J Schorn1, Michael J Gutbrod2, Chantal LeBlanc3
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Cell
|July 1, 2017
概括
称为tRNA衍生片段 (tRF) 的小RNA通过向其复制机制来抑制内源逆转录病毒 (ERV). 这一发现揭示了一种控制细胞中转子子活动的新机制.
科学领域:
- 分子生物学
- 遗传学
- 表观遗传学
背景情况:
- 在细胞重编程过程中,当表观遗传沉默丢失时,转位子的重新激活会带来风险.
- 长终端重复 (LTR) - 逆转移体或内源逆转移体 (ERV) 是小鼠细胞中缺乏特定基因组修饰的新插入的主要来源.
研究的目的:
- 研究tRNA衍生小RNAs (tRFs) 在控制内源逆转录病毒 (ERV) 活动中的作用.
- 确定tRFs调节逆转移子移动性的具体目标和机制.
主要方法:
- 在植入前干细胞中分析小RNA群.
- 在体外逆转换试验以评估tRFs的ERV抑制.
- 在ERV序列中识别tRNA衍生的小RNA (tRF) 目标.
主要成果:
- 鉴定出大量的18nt和无处不在的22nt的tRF.
- 这些tRF针对ERV逆转录的基本结合点 (PBS).
- tRFs显著抑制了主要ERV家族的逆转换 (IAP,MusD/ ETn).
结论:
- 通过干扰 ERV 复制,tRF 作为对转子子重新激活的防御机制.
- 22 nt tRF 在转录后沉默编码ERV,而18 nt tRF 抑制反转录和移动性.
- 向PBS是一种抑制LTR逆转移子的特定策略,表明一个保留的小RNA介导的转移子控制机制.
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