The search for endogenous siRNAs in the mammalian brain.
The search for endogenous siRNAs in the mammalian brain.
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DOI：
10.1016/j.expneurol.2011.10.015
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发表时间：
2012-06
影响因子：
5.3
通讯作者：
Smalheiser, Neil R.
中科院分区：
文献类型：
--
作者：
Smalheiser, Neil R.
十年前，RNA干扰被提出作为调节哺乳动物大脑中长期基因表达的生理手段。然而，在此期间，这一假设似乎与实验数据和理论考虑相矛盾。最近，深度测序技术的出现允许重新评估这个问题。如本文所述，在成年小鼠海马内检测到大量具有内源性siRNA特征的小RNA，其来源于参与突触结构和信号传导的基因，并且在嗅觉辨别训练期间显示出显著但适度（16-22%）的上调。还检测到来源于丰富的细胞非编码RNA的小RNA;特别是25-30 nt的RNA亚群。在嗅觉辨别训练期间，长度显示非常大的（>100倍）上调。初步数据表明，25-30 nt。RNA可能与MIWI而不是Argonaute 1-4同源物相关。我的结论是，尽管他们明显的低丰度，内源性siRNA和非编码RNA衍生的小RNA可能发挥重要作用，在调节突触可塑性。
A decade ago, RNA interference was proposed to serve as a physiologic means of regulating long-term gene expression in the mammalian brain. However, during the intervening years, this hypothesis appeared to be contradicted by both experimental data and theoretical considerations. More recently, the advent of deep sequencing technology has permitted a re-assessment of this issue. As reviewed here, a large population of small RNAs having features characteristic of endogenous siRNAs are detected within adult mouse hippocampus, which derive from genes involved in synaptic structure and signaling, and which show a significant, though modest (16–22%) up-regulation during olfactory discrimination training. Small RNAs derived from abundant cellular noncoding RNAs are also detected; in particular, a subpopulation of RNAs 25–30 nt. in length shows very large (>100 fold) up-regulation during olfactory discrimination training. Preliminary data suggest that the 25–30 nt. RNAs may associate with MIWI rather than Argonaute 1–4 homologues. I conclude that, despite their apparent low abundance, endogenous siRNAs and noncoding RNA-derived small RNAs are likely to play an important role in regulating synaptic plasticity.
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