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Open AccessReview

Is the Efficiency of RNA Silencing Evolutionarily Regulated?

by Kumiko Ui-Tei 1,2
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
Academic Editor: Y-h. Taguchi
Int. J. Mol. Sci. 2016, 17(5), 719;
Received: 12 April 2016 / Revised: 6 May 2016 / Accepted: 9 May 2016 / Published: 12 May 2016
(This article belongs to the Special Issue MicroRNA Regulation)
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. View Full-Text
Keywords: RNA silencing; siRNA; miRNA; silencing efficiency; base-pairing stability; thermodynamic stability RNA silencing; siRNA; miRNA; silencing efficiency; base-pairing stability; thermodynamic stability
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Ui-Tei, K. Is the Efficiency of RNA Silencing Evolutionarily Regulated? Int. J. Mol. Sci. 2016, 17, 719.

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