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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Molecular Evidence of Cryptotanshinone for Treatment and Prevention of Human Cancer
Anti-Cancer Agents in Medicinal Chemistry Quinones Derived from Plant Secondary Metabolites as Anti-cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Xeno-Cannibalism as an Exacerbation of Self-Cannibalism: A Possible Fruitful Survival Strategy for Cancer Cells
Current Pharmaceutical Design Biomolecules Linked to Transition Metal Complexes - New Chances for Chemotherapy
Current Medicinal Chemistry Post-Translational Modifications of PTEN and their Potential Therapeutic Implications
Current Cancer Drug Targets Carbonic Anhydrase Inhibitors and the Management of Cancer
Current Topics in Medicinal Chemistry Recurrent Left Atrial Low-grade Malignant Inflammatory Myofibroblastic Tumor Characterized by Cardiovascular Magnetic Resonance
Current Medical Imaging Green Tea Catechins as Novel Antitumor and Antiangiogenic Compounds
Current Medicinal Chemistry - Anti-Cancer Agents Histone Deacetylase Inhibitors and Anticancer Therapy
Current Medicinal Chemistry - Anti-Cancer Agents Current Gene Expression Studies in Esophageal Carcinoma
Current Genomics Blind Snipers: Relevant Off Target Effects of Non-chemotherapeutic Agents in Oncology: Review of the Literature
Reviews on Recent Clinical Trials Renaissance of the Biologically Active Vitamin A Derivatives: Established and Novel Directed Therapies for Cancer and Chemoprevention
Current Pharmaceutical Design Application and Future Prospect of Extracellular Matrix Targeted Nanomaterials in Tumor Theranostics
Current Drug Targets Vitamin D3 and Vitamin D3 Analogues as an Adjunct to Cancer Chemotherapy and Radiotherapy
Current Medicinal Chemistry - Anti-Cancer Agents Androgen Pathway Related Gene Variants and Prostate Cancer Association in Auckland Men
Current Pharmacogenomics and Personalized Medicine Cause and Consequences of Genetic and Epigenetic Alterations in Human Cancer
Current Genomics A Simple and Reliable Approach for Assessing Anticancer Activity In Vitro
Current Medicinal Chemistry Choline Kinase Active Site Provides Features for Designing Versatile Inhibitors
Current Topics in Medicinal Chemistry Carbon Nanotubes in the Diagnosis and Treatment of Malignant Melanoma
Anti-Cancer Agents in Medicinal Chemistry Vinorelbine in Cancer Therapy
Current Drug Targets