MicroRNAs (miRNAs) are short (∼22 nucleotides) regulators of gene expression acting by direct base pairing to 3'-UTR target sites in messenger RNAs. Mature miRNAs are produced by two sequential endonucleolytic cleavages facilitated by Drosha in the nucleus and Dicer in the cytoplasm. A subclass of miRNAs, termed mirtrons, derives from short introns and enters the miRNA biogenesis pathway as Dicer substrates. Here we uncover a third biogenesis strategy that, similar to mirtron biogenesis, initiates from short introns but bypasses Dicer cleavage. These short introns (80-100 nucleotides), coined agotrons, are associated with and stabilized by Argonaute (Ago) proteins in the cytoplasm. Some agotrons are completely conserved in mammalian species, suggesting that they are functionally important. Furthermore, we demonstrate that the agotrons are capable of repressing mRNAs with seed-matching target sequences in the 3'-UTR. These data provide evidence for a novel RNA regulator of gene expression, which bypasses the canonical miRNA biogenesis machinery.

中文翻译：

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Argonaute相关的短内含子是一类新型的基因调节子。

MicroRNA（miRNA）是短基因（〜22个核苷酸），通过与信使RNA中的3'-UTR目标位点直接碱基配对而起作用。成熟的miRNA由细胞核中的Drosha和细胞质中的Dicer促进的两个连续的内切核酸酶裂解产生。miRNA的一个亚类，称为mirtrons，源于短内含子，并以Dicer底物的形式进入miRNA生物发生途径。在这里，我们揭示了第三个生物生成策略，类似于mirtron的生物生成，它是从短内含子开始但绕过Dicer切割的。这些短的内含子（80-100个核苷酸），造就的agotrons，与细胞质中的Argonaute（Ago）蛋白相关并被其稳定。在哺乳动物物种中，某些原子反应堆是完全保守的，这表明它们在功能上很重要。此外，我们证明，agotrons能够抑制3'-UTR中具有种子匹配靶序列的mRNA。这些数据为新型的基因表达RNA调节剂提供了证据，该调节剂绕过了典型的miRNA生物发生机制。