Facilitator oligonucleotides increase ribozyme RNA binding to full-length RNA substrates in vitro

FEBS Letters
R B Denman

Abstract

Primer extension arrest (PEA) studies have demonstrated that antisense oligonucleotides (beta 112C, beta 114C), which lie upstream of a ribozyme targeted to beta-amyloid peptide precursor (beta APP) mRNA, but not sense oligonucleotides (beta 112S, beta 116S) or a scrambled oligonucleotide, beta 116 M, affect ribozyme-mediated cleavage in vitro. Substrate dissociation experiments revealed that the ribozyme binding site in this mRNA was masked; PEA kinetics showed the association of the ribozyme and substrate was enhanced by antisense oligonucleotide binding. These studies suggest that masked ribozyme cleavage sites that may occur in disease-causing mRNAs can be targeted for degradation using "facilitator" oligonucleotides.

References

Dec 8, 1992·Biochemistry·M J Fedor, O C Uhlenbeck
Jul 31, 1992·Biochemical and Biophysical Research Communications·R B DenmanD L Miller
Mar 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M J Fedor, O C Uhlenbeck
Mar 9, 1990·Science·N SarverJ J Rossi
Aug 13, 1987·Nature·O C Uhlenbeck
Jun 13, 1989·Biochemistry·A Hampel, R Tritz
Jan 1, 1994·Antisense Research and Development·S Nesbitt, J Goodchild
Jun 25, 1994·Nucleic Acids Research·R B DenmanD L Miller
Jul 11, 1993·Nucleic Acids Research·M VenturaS Saragosti
Aug 25, 1993·Nucleic Acids Research·R B Denman
Sep 1, 1993·Archives of Biochemistry and Biophysics·R Denman, D L Miller

❮ Previous
Next ❯

Citations

May 24, 2001·Archives of Biochemistry and Biophysics·N DolzhanskayaR B Denman
Jul 17, 1998·Current Opinion in Chemical Biology·S VermaF Eckstein
May 4, 2001·Antisense & Nucleic Acid Drug Development·E HovigJ Goodchild
Nov 11, 1999·Antisense & Nucleic Acid Drug Development·S Horn, B Schwenzer
Jan 3, 1997·Biochemical and Biophysical Research Communications·R B Denman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.