Genome-wide identification of genes regulated in trans by transposable element small interfering RNAs.

Genome-wide identification of genes regulated in trans by transposable element small interfering RNAs.
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DOI:
10.4161/rna.25555
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发表时间:
2013-08
期刊:
影响因子:
4.1
通讯作者:
Slotkin RK
Slotkin RK
中科院分区:
生物学3区
文献类型:
--
作者:
McCue AD;Nuthikattu S;Slotkin RK

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众所周知,转座元件(TE)可以通过多种机制影响邻近基因的调节。此外,最近发现 TE 可以通过小干扰 RNA (siRNA) 的反式作用性质调节非邻近基因。当 TE 的表观遗传抑制消失时,TE 变得转录活跃,宿主细胞通过将 TE mRNA 降解为 siRNA 来抑制诱变转座。在这项研究中,我们在模式植物拟南芥中进行了全基因组分析,发现基于 TE siRNA 的基因 mRNA 调控比之前两个原理验证示例更为普遍。我们鉴定了 27 个候选基因 mRNA,它们不包含 TE 片段,但通过 TE siRNA 积累的部分互补性进行调节,因此受到 TE 表观遗传激活的影响。我们通过实验证实了几个基因靶标,并证明它们对掺入拟南芥 Argonaute1 蛋白中的特定 21 核苷酸 TE siRNA 的积累有反应。此外,我们发现一种 TE siRNA 特异性靶向并抑制宿主蛋白的形成,从而抑制 TE 活性,这表明 TE 含有并可能在进化上选择短序列作为宿主 TE 抑制的抑制剂。
Transposable elements (TEs) are known to influence the regulation of neighboring genes through a variety of mechanisms. Additionally, it was recently discovered that TEs can regulate non-neighboring genes through the trans-acting nature of small interfering RNAs (siRNAs). When the epigenetic repression of TEs is lost, TEs become transcriptionally active, and the host cell acts to repress mutagenic transposition by degrading TE mRNAs into siRNAs. In this study, we have performed a genome-wide analysis in the model plant Arabidopsis thaliana and found that TE siRNA-based regulation of genic mRNAs is more pervasive than the two formerly characterized proof-of-principle examples. We identified 27 candidate genic mRNAs that do not contain a TE fragment but are regulated through partial complementarity by the accumulation of TE siRNAs and are therefore influenced by TE epigenetic activation. We have experimentally confirmed several gene targets and demonstrated that they respond to the accumulation of specific 21 nucleotide TE siRNAs that are incorporated into the Arabidopsis Argonaute1 protein. Additionally, we found that one TE siRNA specifically targets and inhibits the formation of a host protein that acts to repress TE activity, suggesting that TEs harbor and potentially evolutionarily select short sequences to act as suppressors of host TE repression.
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