Abstract
RNA interference (RNAi) is an evolutionary conserved mechanism by which small double-stranded RNA (dsRNA) — termed small interfering RNA (siRNA) — inhibit translation or degrade complementary mRNA sequences. Identifying features and enzymatic components of the RNAi pathway have led to the design of highly-effective siRNA molecules for laboratory and therapeutic application. RNA activation (RNAa) is a newly discovered mechanism of gene induction also triggered by dsRNAs termed small activating RNA (saRNA). It offers similar benefits as RNA interference (RNAi), while representing a new method of gene overexpression. In the present study, we identify features of RNAa and explore chemical modifications to saRNAs that improve the applicability of RNAa. We evaluate the rate of RNAa activity in order to define an optimal window of gene induction, while comparing the kinetic differences between RNAa and RNAi. We identify Ago2 as a conserved enzymatic component of both RNAa and RNAi implicating that saRNA may tolerate modification based on Ago2 function. As such, we define chemical modifications to saRNAs that manipulate RNAa activity, as well as exploit their effects to design saRNAs with enhanced medicinal properties. These findings reveal functional features of RNAa that may be utilized to augment saRNA function for mechanistic studies or the development of RNAa-based drugs.
Keywords: Argonaute 2 (Ago2), cancer therapeutics, E-cadherin, gene promoter, p21, RNA activation (RNAa), RNA interference (RNAi), small activating RNA (saRNA), small interfering RNA (siRNA), strand modifications
Current Pharmaceutical Biotechnology
Title: Defining Features and Exploring Chemical Modifications to Manipulate RNAa Activity
Volume: 11 Issue: 5
Author(s): Robert F. Place, Emily J. Noonan, Zeno Foldes-Papp and Long-Cheng Li
Affiliation:
Keywords: Argonaute 2 (Ago2), cancer therapeutics, E-cadherin, gene promoter, p21, RNA activation (RNAa), RNA interference (RNAi), small activating RNA (saRNA), small interfering RNA (siRNA), strand modifications
Abstract: RNA interference (RNAi) is an evolutionary conserved mechanism by which small double-stranded RNA (dsRNA) — termed small interfering RNA (siRNA) — inhibit translation or degrade complementary mRNA sequences. Identifying features and enzymatic components of the RNAi pathway have led to the design of highly-effective siRNA molecules for laboratory and therapeutic application. RNA activation (RNAa) is a newly discovered mechanism of gene induction also triggered by dsRNAs termed small activating RNA (saRNA). It offers similar benefits as RNA interference (RNAi), while representing a new method of gene overexpression. In the present study, we identify features of RNAa and explore chemical modifications to saRNAs that improve the applicability of RNAa. We evaluate the rate of RNAa activity in order to define an optimal window of gene induction, while comparing the kinetic differences between RNAa and RNAi. We identify Ago2 as a conserved enzymatic component of both RNAa and RNAi implicating that saRNA may tolerate modification based on Ago2 function. As such, we define chemical modifications to saRNAs that manipulate RNAa activity, as well as exploit their effects to design saRNAs with enhanced medicinal properties. These findings reveal functional features of RNAa that may be utilized to augment saRNA function for mechanistic studies or the development of RNAa-based drugs.
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Cite this article as:
F. Place Robert, J. Noonan Emily, Foldes-Papp Zeno and Li Long-Cheng, Defining Features and Exploring Chemical Modifications to Manipulate RNAa Activity, Current Pharmaceutical Biotechnology 2010; 11 (5) . https://dx.doi.org/10.2174/138920110791591463
DOI https://dx.doi.org/10.2174/138920110791591463 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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