The Coding Regions of Germline mRNAs Confer Sensitivity to Argonaute Regulation in C. elegans.
The Coding Regions of Germline mRNAs Confer Sensitivity to Argonaute Regulation in C. elegans.
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DOI：
10.1016/j.celrep.2018.02.009
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发表时间：
2018-02-27
期刊：
影响因子：
8.8
通讯作者：
Mello CC
中科院分区：
文献类型：
--
作者：
Seth M;Shirayama M;Tang W;Shen EZ;Tu S;Lee HC;Weng Z;Mello CC
蛋白质编码基因与非编码区的因子进行广泛的调控相互作用。相反，开放阅读框（ORF）被认为受到编码功能的限制，从而排除了在基因调控中的主要作用。在这里，我们探讨Piwi相互作用（pi）RNA介导的转基因沉默在C。elegans中，并显示对皮尔纳沉默的敏感性的显著差异映射到转基因ORF内的内源序列。在抗性转基因的ORF内牺牲性地增加皮尔纳靶向可以导致表达的部分但稳定的降低，揭示了piRNA不仅沉默而且还可以“调节”基因表达。我们的研究结果支持了一种模型，该模型涉及生殖系Argonautes的mRNA调控的时间元件，可能在翻译之前，并表明piRNA通过靶向mRNA的主体（包括编码区）来提供生殖系mRNA表达的增量控制。一些C。线虫转基因抵抗皮尔纳沉默。Seth等人绘制了转基因内内源序列的抗性图，并表明人工增加皮尔纳靶向可以在不沉默的情况下逐渐减少表达。他们的发现将编码区域确定为核周核内丰富的皮尔纳调控景观的一部分。
Protein-coding genes undergo a wide array of regulatory interactions with factors that engage non-coding regions. Open reading frames (ORFs), in contrast, are thought to be constrained by coding function, precluding a major role in gene regulation. Here, we explore Piwi-interacting (pi)RNA-mediated transgene silencing in C. elegans and show that marked differences in the sensitivity to piRNA silencing map to the endogenous sequences within transgene ORFs. Artificially increasing piRNA targeting within the ORF of a resistant transgene can lead to a partial yet stable reduction in expression, revealing that piRNAs not only silence but can also “tune” gene expression. Our findings support a model that involves a temporal element to mRNA regulation by germline Argonautes, likely prior to translation, and suggest that piRNAs afford incremental control of germline mRNA expression by targeting the body of the mRNA, including the coding region. Some C. elegans transgenes resist piRNA silencing. Seth et al. map resistance to endogenous sequences within transgenes and show that artificially increasing piRNA targeting can incrementally reduce expression without silencing. Their findings identify coding regions as part of a rich piRNA regulatory landscape within perinuclear nuage.
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影响因子：
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通讯作者：
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