RNA-protein hybrid ribozymes that efficiently cleave any mRNA independently of the structure of the target RNA

Proceedings of the National Academy of Sciences of the United States of America
M WarashinaK Taira

Abstract

Ribozyme activity in vivo depends on achieving high-level expression, intracellular stability, target colocalization, and cleavage site access. At present, target site selection is problematic because of unforeseeable secondary and tertiary RNA structures that prevent cleavage. To overcome this design obstacle, we wished to engineer a ribozyme that could access any chosen site. To create this ribozyme, the constitutive transport element (CTE), an RNA motif that has the ability to interact with intracellular RNA helicases, was attached to our ribozymes so that the helicase-bound, hybrid ribozymes would be produced in cells. This modification significantly enhanced ribozyme activity in vivo, permitting cleavage of sites previously found to be inaccessible. To confer cleavage enhancement, the CTE must retain helicase-binding activity. Binding experiments demonstrated the likely involvement of RNA helicase(s). We found that attachment of the RNA motif to our tRNA ribozymes leads to cleavage in vivo at the chosen target site regardless of the local RNA secondary or tertiary structure.

References

Jan 1, 1992·Annual Review of Biochemistry·R H Symons
Jan 31, 1995·Proceedings of the National Academy of Sciences of the United States of America·M YuF Wong-Staal
Feb 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·M BrayM L Hammarskjöld
Dec 6, 1996·Journal of Molecular Biology·M C YoungP H von Hippel
Apr 1, 1997·European Journal of Biochemistry·K R BirikhF Eckstein
Jun 1, 1997·Nature Biotechnology·N MilnerE M Southern
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·D Plehn-Dujowich, S Altman
Oct 27, 1998·Nature Biotechnology·T KuwabaraK Taira
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·J LiF Wong-Staal
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·T KuwabaraK Taira
May 14, 1999·Trends in Biochemical Sciences·J de la CruzP Linder
Apr 5, 2000·The Journal of Biological Chemistry·C WestbergF Wong-Staal
Aug 22, 2000·Nature·T TanabeS Asano

❮ Previous
Next ❯

Citations

May 16, 2006·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Sen QiaXiaoping Chen
Apr 8, 2004·Virus Research·Makoto MiyagishiKazunari Taira
Nov 5, 2002·Trends in Biotechnology·Michael Famulok, Sandeep Verma
Jul 27, 2002·Journal of Biotechnology·Louis-Marie Houdebine
Feb 22, 2003·Biochimie·Louis-Marie Houdebine
Sep 6, 2003·Gene·Stephen M L Raj, Fenyong Liu
Jun 16, 2005·Nature Reviews. Molecular Cell Biology·Hideo AkashiKazunari Taira
Feb 12, 2008·Proceedings of the National Academy of Sciences of the United States of America·Eirik W LundbladSidney Altman
Aug 22, 2009·Journal of Toxicology and Environmental Health. Part a·Michael J StobartJ David Knox
Dec 13, 2002·Antisense & Nucleic Acid Drug Development·Masayuki SanoKazunari Taira
Mar 6, 2004·Oligonucleotides·Makoto Miyagishi, Kazunari Taira
Sep 4, 2004·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Custer C DeocarisRenu Wadhwa
Feb 6, 2004·Nucleic Acids Research·Koichi YoshinariKazunari Taira
Aug 20, 2009·RNA·Andreas PlonerAlexander Hüttenhofer
May 17, 2003·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·David SteeleGarrett A Soukup
Feb 22, 2005·Mechanisms of Ageing and Development·Renu WadhwaSunil C Kaul
Sep 13, 2005·Biochemical and Biophysical Research Communications·Surintorn BoonanuntanasarnGoro Yoshizaki
Apr 7, 2004·Differentiation; Research in Biological Diversity·Hiroaki KawasakiKazunari Taira
Apr 17, 2003·FEMS Microbiology Reviews·Elena Puerta-FernándezAlfredo Berzal-Herranz
Jun 30, 2015·Current Opinion in Insect Science·Alexander W E FranzMalcolm J Fraser
Feb 8, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wei-Hua PanGary A Clawson
Apr 20, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wei-Hua PanGary A Clawson
Sep 2, 2003·The Journal of Gene Medicine·Seiya HagiwaraYoshiro Niitsu
Sep 28, 2004·The Journal of Biological Chemistry·Renu WadhwaSunil C Kaul
Dec 14, 2001·The Journal of Biological Chemistry·Venkat GopalanSidney Altman
Jun 18, 2005·Journal of Receptor and Signal Transduction Research·Hidehisa ShimizuHitoshi Miyazaki

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.