MGH Cancer Center, Harvard Medical School, Boston, MA, USA.
Wiley Interdiscip Rev RNA. 2012 May-Jun;3(3):311-30. doi: 10.1002/wrna.121. Epub 2011 Nov 9.
MicroRNAs are small non-coding RNA guide molecules that regulate gene expression via association with effector complexes and sequence-specific recognition of target sites on other RNAs; misregulated microRNA expression and functions are linked to a variety of tumors, developmental disorders, and immune disease. MicroRNAs have primarily been demonstrated to mediate posttranscriptional downregulation of expression; translational repression, and deadenylation-dependent decay of messages through partially complementary microRNA target sites in mRNA untranslated regions (UTRs). However, an emerging assortment of studies, discussed in this review, reveal that microRNAs and their associated protein complexes (microribonucleoproteins or microRNPs) can additionally function to posttranscriptionally stimulate gene expression by direct and indirect mechanisms. These reports indicate that microRNA-mediated effects can be selective, regulated by the RNA sequence context, and associated with RNP factors and cellular conditions. Like repression, translation upregulation by microRNAs has been observed to range from fine-tuning effects to significant alterations in expression. These studies uncover remarkable, new abilities of microRNAs and associated microRNPs in gene expression control and underscore the importance of regulation, in cis and trans, in directing appropriate microRNP responses.
微小 RNA 是一种小型非编码 RNA 引导分子，通过与效应因子复合物结合，并特异性识别其他 RNA 上的靶位点来调节基因表达；微小 RNA 表达和功能的失调与多种肿瘤、发育障碍和免疫性疾病有关。微小 RNA 主要被证明可以通过在 mRNA 非翻译区（UTR）中的部分互补微小 RNA 靶位点介导转录后表达下调、翻译抑制和依赖脱腺苷酸化的信使降解。然而，本综述中讨论的一系列新出现的研究表明，微小 RNA 及其相关的蛋白质复合物（微核糖核蛋白或 microRNPs）还可以通过直接和间接机制，在后转录水平上刺激基因表达。这些报告表明，微小 RNA 介导的效应可以是选择性的，受 RNA 序列上下文的调节，并与 RNP 因子和细胞状态有关。与抑制作用类似，微小 RNA 引起的翻译上调范围从精细调节效应到表达的显著改变。这些研究揭示了微小 RNA 和相关 microRNPs 在基因表达控制中的显著新功能，并强调了顺式和反式调控在指导适当的 microRNP 反应中的重要性。
