LTR-Retrotransposon Control by tRNA-Derived Small RNAs.

LTR-Retrotransposon Control by tRNA-Derived Small RNAs.
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DOI:
10.1016/j.cell.2017.06.013
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发表时间:
2017-06-29
期刊:
影响因子:
64.5
通讯作者:
Martienssen R
Martienssen R
中科院分区:
生物学1区
文献类型:
--
作者:
Schorn AJ;Gutbrod MJ;LeBlanc C;Martienssen R

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转座子再激活是在发育重编程期间失去表观遗传沉默的细胞中的固有危险。在小鼠中,LTR-逆转录转座子或内源性逆转录病毒(ERV)解释了大多数新的插入,并且在植入前干细胞中不存在组蛋白H3赖氨酸9三甲基化的情况下表达。我们在这些细胞中发现了丰富的18 nt tRNA衍生的小RNA(tRF),并且普遍表达22 nt tRF,其包括成熟tRNA的3′末端CCA,并且靶向ERV逆转录所必需的tRNA引物结合位点(PBS)。我们发现,两个最活跃的ERV家族,IAP和MusD/ETn,是主要的目标,并强烈抑制逆转录转座试验中的tRFs。22 nt tRFs转录后沉默编码能力ERVs,而18 nt tRFs特异性干扰逆转录和逆转录转座子移动性。PBS提供了特异性抑制LTR-逆转录转座子的独特靶标,并且tRF靶向是小RNA介导的转座子控制的潜在高度保守机制。3′ tRNA片段限制转座因子在小鼠ES细胞中的迁移
Transposon reactivation is an inherent danger in cells that lose epigenetic silencing during developmental reprogramming. In the mouse, LTR-retrotransposons, or endogenous retroviruses (ERV), account for most novel insertions and are expressed in the absence of histone H3 Lysine 9 trimethylation in preimplantation stem cells. We found abundant, 18 nt tRNA-derived small RNA (tRF) in these cells, and ubiquitously expressed 22 nt tRFs, that include the 3′ terminal CCA of mature tRNAs, and target the tRNA primer binding site (PBS) essential for ERV reverse transcription. We show that the two most active ERV families, IAP and MusD/ETn, are major targets and are strongly inhibited by tRFs in retrotransposition assays. 22 nt tRFs post-transcriptionally silence coding-competent ERVs, while 18 nt tRFs specifically interfere with reverse transcription and retrotransposon mobility. The PBS offers a unique target to specifically inhibit LTR-retrotransposons and tRF-targeting is a potentially highly conserved mechanism of small RNA-mediated transposon control. 3′ tRNA fragments limit the mobility of transposable elements in mouse ES cells
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