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腾讯登录Nature：发现microRNA可调节自身表达
| 导读 | MicroRNA家族成员对基因表达的转录后调节有重要作用，参与着很多生物学过程。大多数的microRNA是通过Drosha和Dicer的加工得来的，Drosha将长链的原始转录本剪切成约含有颈环结构的65个碱基的microRNA前体，再由Dicer将其加工为含有约22个碱基的双链成熟microRNA。成熟的microRNA与Argonaute蛋白复合体结合，通过不完全配对靶向mRNA，阻遏翻译。
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MicroRNA家族成员对基因表达的转录后调节有重要作用，参与着很多生物学过程。大多数的microRNA是通过Drosha和Dicer的加工得来的，Drosha将长链的原始转录本剪切成约含有颈环结构的65个碱基的microRNA前体，再由Dicer将其加工为含有约22个碱基的双链成熟microRNA。成熟的microRNA与Argonaute蛋白复合体结合，通过不完全配对靶向mRNA，阻遏翻译。
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本文的研究者发现，microRNA复合体也能靶向非编码RNA并对其进行调节。实验表明，在秀丽新小杆线虫中，Argonaute家族的ALG-1蛋白特异性的结合在microRNAlet-7原始转录本的3'端，并调节下游的生物学事件。而介导这一过程的正是let-7本身。进一步研究证明，在人体中，ALG-1也能与let-7的原始转录本结合。这一研究阐述了一种microRNA新的作用机制，即microRNA除了靶向mRNA调节翻译外，还可以靶向非编码RNA对自身的表达进行反馈调节。
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<a title="" href="http://dx.doi.org/10.1038/nature11134" target="_blank">doi:10.1038/nature11134</a>
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<br/><strong>Autoregulation of microRNA biogenesis by <em>let-7</em> and Argonaute</strong><br/>
Dimitrios G. Zisoulis, Zoya S. Kai, Roger K. Chang & Amy E. Pasquinelli.
MicroRNAs (miRNAs) comprise a large family of small RNA molecules that post-transcriptionally regulate gene expression in many biological pathways1. Most miRNAs are derived from long primary transcripts that undergo processing by Drosha to produce ~65-nucleotide precursors that are then cleaved by Dicer, resulting in the mature 22-nucleotide forms2, 3. Serving as guides in Argonaute protein complexes, mature miRNAs use imperfect base pairing to recognize sequences in messenger RNA transcripts, leading to translational repression and destabilization of the target messenger RNAs4, 5. Here we show that the miRNA complex also targets and regulates non-coding RNAs that serve as substrates for the miRNA-processing pathway. We found that the Argonaute protein in Caenorhabditis elegans, ALG-1, binds to a specific site at the 3′ end of <em>let-7</em> miRNA primary transcripts and promotes downstream processing events. This interaction is mediated by mature <em>let-7</em> miRNA through a conserved complementary site in its own primary transcript, thus creating a positive-feedback loop. We further show that ALG-1 associates with <em>let-7</em> primary transcripts in nuclear fractions. Argonaute also binds <em>let-7</em> primary transcripts in human cells, demonstrating that the miRNA pathway targets non-coding RNAs in addition to protein-coding messenger RNAs across species. Moreover, our studies in C. elegans reveal a novel role for Argonaute in promoting biogenesis of a targeted transcript, expanding the functions of the miRNA pathway in gene regulation. This discovery of autoregulation of <em>let-7</em> biogenesis establishes a new mechanism for controlling miRNA expression.
<br/>来源：生物谷
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本文的研究者发现，microRNA复合体也能靶向非编码RNA并对其进行调节。实验表明，在秀丽新小杆线虫中，Argonaute家族的ALG-1蛋白特异性的结合在microRNAlet-7原始转录本的3'端，并调节下游的生物学事件。而介导这一过程的正是let-7本身。进一步研究证明，在人体中，ALG-1也能与let-7的原始转录本结合。这一研究阐述了一种microRNA新的作用机制，即microRNA除了靶向mRNA调节翻译外，还可以靶向非编码RNA对自身的表达进行反馈调节。
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<div>
<div>
<img id="cover-image" src="http://www.bioon.com/biology/UploadFiles/201206/20120602210321699.jpg" alt="" width="116" />
<a title="" href="http://dx.doi.org/10.1038/nature11134" target="_blank">doi:10.1038/nature11134</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Autoregulation of microRNA biogenesis by <em>let-7</em> and Argonaute</strong><br/>
Dimitrios G. Zisoulis, Zoya S. Kai, Roger K. Chang & Amy E. Pasquinelli.
MicroRNAs (miRNAs) comprise a large family of small RNA molecules that post-transcriptionally regulate gene expression in many biological pathways1. Most miRNAs are derived from long primary transcripts that undergo processing by Drosha to produce ~65-nucleotide precursors that are then cleaved by Dicer, resulting in the mature 22-nucleotide forms2, 3. Serving as guides in Argonaute protein complexes, mature miRNAs use imperfect base pairing to recognize sequences in messenger RNA transcripts, leading to translational repression and destabilization of the target messenger RNAs4, 5. Here we show that the miRNA complex also targets and regulates non-coding RNAs that serve as substrates for the miRNA-processing pathway. We found that the Argonaute protein in Caenorhabditis elegans, ALG-1, binds to a specific site at the 3′ end of <em>let-7</em> miRNA primary transcripts and promotes downstream processing events. This interaction is mediated by mature <em>let-7</em> miRNA through a conserved complementary site in its own primary transcript, thus creating a positive-feedback loop. We further show that ALG-1 associates with <em>let-7</em> primary transcripts in nuclear fractions. Argonaute also binds <em>let-7</em> primary transcripts in human cells, demonstrating that the miRNA pathway targets non-coding RNAs in addition to protein-coding messenger RNAs across species. Moreover, our studies in C. elegans reveal a novel role for Argonaute in promoting biogenesis of a targeted transcript, expanding the functions of the miRNA pathway in gene regulation. This discovery of autoregulation of <em>let-7</em> biogenesis establishes a new mechanism for controlling miRNA expression.
<br/>来源：生物谷
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