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Place, RF; Noonan, EJ; Földes-Papp, Z; Li, LC.
Defining features and exploring chemical modifications to manipulate RNAa activity.
Curr Pharm Biotechnol. 2010; 11(5):518-526 Doi: 10.2174/138920110791591463 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Földes-Papp Zeno
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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.
Find related publications in this database (using NLM MeSH Indexing)
Genetic Engineering - methods
RNA, Small Interfering - chemistry RNA, Small Interfering - genetics

Find related publications in this database (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
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