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RNA沉默的效率是否受到进化调控？

Is the Efficiency of RNA Silencing Evolutionarily Regulated?

作者信息

Ui-Tei Kumiko

机构信息

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba-ken 277-8561, Japan.

出版信息

Int J Mol Sci. 2016 May 12;17(5):719. doi: 10.3390/ijms17050719.

DOI:10.3390/ijms17050719
PMID:27187367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4881541/
Abstract

Small interfering RNAs (siRNAs) and microRNAs (miRNAs) regulate gene expression in a sequence-specific manner. Genes with partial complementarity to siRNA/miRNA sequences in their 3'-untranslated regions (UTRs) are suppressed by a mechanism referred to as the siRNA off-target effect or miRNA-mediated RNA silencing. However, the determinants of such RNA silencing efficiency are poorly understood. Previously, I and co-workers reported that the efficiency of RNA silencing is strongly correlated with the thermodynamic stability of base pairing in the duplex formed within an siRNA/miRNA and between the seed region and its target mRNA. In this review, I first summarize our previous studies that identified the thermodynamic parameter to estimate the silencing efficiency using the calculated base pairing stability: siRNAs downregulate the expression of off-target genes depending on the stability of binding between the siRNA seed region (nucleotides 2-8) and off-target mRNAs, and miRNAs downregulate target mRNA expression depending on the stability of the duplex formed between the 5' terminus of the miRNA and its target mRNA. I further discuss the possibility that such thermodynamic features of silencing efficiency may have arisen during evolution with increasing body temperature in various organisms.

摘要

小干扰RNA（siRNA）和微小RNA（miRNA）以序列特异性方式调节基因表达。在其3'非翻译区（UTR）与siRNA/miRNA序列具有部分互补性的基因，会通过一种称为siRNA脱靶效应或miRNA介导的RNA沉默的机制受到抑制。然而，这种RNA沉默效率的决定因素却知之甚少。此前，我和同事报道，RNA沉默效率与在siRNA/miRNA内形成的双链体以及种子区域与其靶标mRNA之间形成的碱基配对的热力学稳定性密切相关。在这篇综述中，我首先总结我们之前的研究，这些研究利用计算出的碱基配对稳定性确定了用于估计沉默效率的热力学参数：siRNA根据其种子区域（核苷酸2-8）与脱靶mRNA之间结合的稳定性下调脱靶基因的表达，而miRNA则根据miRNA 5'末端与其靶标mRNA之间形成的双链体的稳定性下调靶标mRNA的表达。我还进一步讨论了随着各种生物体体温升高，这种沉默效率的热力学特征可能在进化过程中出现的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0a/4881541/2c6d8f625943/ijms-17-00719-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0a/4881541/fcb87054ba63/ijms-17-00719-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0a/4881541/3052e7345814/ijms-17-00719-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0a/4881541/f943d6c2628d/ijms-17-00719-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0a/4881541/2c6d8f625943/ijms-17-00719-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0a/4881541/fcb87054ba63/ijms-17-00719-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0a/4881541/3052e7345814/ijms-17-00719-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0a/4881541/f943d6c2628d/ijms-17-00719-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0a/4881541/2c6d8f625943/ijms-17-00719-g004.jpg

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2
Stability of miRNA 5'terminal and seed regions is correlated with experimentally observed miRNA-mediated silencing efficacy.miRNA 5'端和种子区的稳定性与实验观察到的 miRNA 介导的沉默效果相关。
Sci Rep. 2012;2:996. doi: 10.1038/srep00996. Epub 2012 Dec 18.
3
Practical Aspects of microRNA Target Prediction.
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Int J Med Sci. 2018 Jan 19;15(4):309-322. doi: 10.7150/ijms.23215. eCollection 2018.
4
Modeling the interactions of sense and antisense Period transcripts in the mammalian circadian clock network.在哺乳动物生物钟网络中模拟有义和反义 Period 转录本的相互作用。
PLoS Comput Biol. 2018 Feb 15;14(2):e1005957. doi: 10.1371/journal.pcbi.1005957. eCollection 2018 Feb.
miRNA 靶基因预测的实用方法。
Curr Mol Med. 2011 Mar;11(2):93-109. doi: 10.2174/156652411794859250.
4
Computational prediction and experimental validation of evolutionarily conserved microRNA target genes in bilaterian animals.后生动物中进化保守的 microRNA 靶基因的计算预测和实验验证。
BMC Genomics. 2010 Feb 9;11:101. doi: 10.1186/1471-2164-11-101.
5
ATP-dependent human RISC assembly pathways.依赖于 ATP 的人类 RISCs 组装途径。
Nat Struct Mol Biol. 2010 Jan;17(1):17-23. doi: 10.1038/nsmb.1733. Epub 2009 Dec 6.
6
Structural determinants of miRNAs for RISC loading and slicer-independent unwinding.微小RNA（miRNA）用于RNA诱导沉默复合体（RISC）加载和不依赖核酸酶切割的解旋的结构决定因素。
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7
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8
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Cell. 2009 Jan 23;136(2):215-33. doi: 10.1016/j.cell.2009.01.002.
9
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Exp Cell Res. 2008 Aug 15;314(14):2618-33. doi: 10.1016/j.yexcr.2008.06.002. Epub 2008 Jun 7.