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Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells
Small noncoding RNAs (ncRNAs) have been shown to guide epigenetic silencing complexes to target loci in human cells. When targeted to gene promoters, these small RNAs can lead to long-term stable epigenetic silencing of gene transcription. To date, small RNAs have been shown to modulate transcriptio...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381641/ https://www.ncbi.nlm.nih.gov/pubmed/23343927 http://dx.doi.org/10.1038/mtna.2012.8 |
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author | Knowling, Stuart Stapleton, Kenneth Turner, Anne-Marie W Uhlmann, Eugen Lehmann, Thomas Vollmer, Jörg Morris, Kevin V |
author_facet | Knowling, Stuart Stapleton, Kenneth Turner, Anne-Marie W Uhlmann, Eugen Lehmann, Thomas Vollmer, Jörg Morris, Kevin V |
author_sort | Knowling, Stuart |
collection | PubMed |
description | Small noncoding RNAs (ncRNAs) have been shown to guide epigenetic silencing complexes to target loci in human cells. When targeted to gene promoters, these small RNAs can lead to long-term stable epigenetic silencing of gene transcription. To date, small RNAs have been shown to modulate transcriptional gene silencing (TGS) of human immunodeficiency virus type 1 (HIV-1) as well as several other disease-related genes, but it has remained unknown as to what extent particular chemistries can be used to generate single-stranded backbone-modified oligonucleotides that are amenable to this form of gene targeting and regulation. Here, we present data indicating that specific combinations of backbone modifications can be used to generate single-stranded antisense oligonucleotides that can functionally direct TGS of HIV-1 in a manner that is however, independent of epigenetic changes at the target loci. Furthermore, this functionality appears contingent on the absence of a 5′ phosphate in the oligonucleotide. These data suggest that chemically modified oligonucleotide based approaches could be implemented as a means to regulate gene transcription in an epigenetically independent manner. |
format | Online Article Text |
id | pubmed-3381641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-33816412012-07-03 Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells Knowling, Stuart Stapleton, Kenneth Turner, Anne-Marie W Uhlmann, Eugen Lehmann, Thomas Vollmer, Jörg Morris, Kevin V Mol Ther Nucleic Acids Original Article Small noncoding RNAs (ncRNAs) have been shown to guide epigenetic silencing complexes to target loci in human cells. When targeted to gene promoters, these small RNAs can lead to long-term stable epigenetic silencing of gene transcription. To date, small RNAs have been shown to modulate transcriptional gene silencing (TGS) of human immunodeficiency virus type 1 (HIV-1) as well as several other disease-related genes, but it has remained unknown as to what extent particular chemistries can be used to generate single-stranded backbone-modified oligonucleotides that are amenable to this form of gene targeting and regulation. Here, we present data indicating that specific combinations of backbone modifications can be used to generate single-stranded antisense oligonucleotides that can functionally direct TGS of HIV-1 in a manner that is however, independent of epigenetic changes at the target loci. Furthermore, this functionality appears contingent on the absence of a 5′ phosphate in the oligonucleotide. These data suggest that chemically modified oligonucleotide based approaches could be implemented as a means to regulate gene transcription in an epigenetically independent manner. Nature Publishing Group 2012-04 2012-04-10 /pmc/articles/PMC3381641/ /pubmed/23343927 http://dx.doi.org/10.1038/mtna.2012.8 Text en Copyright © 2012 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/3.0/ Molecular Therapy-Nucleic Acids is an open-access journal published by Nature Publishing Group. This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Knowling, Stuart Stapleton, Kenneth Turner, Anne-Marie W Uhlmann, Eugen Lehmann, Thomas Vollmer, Jörg Morris, Kevin V Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells |
title | Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells |
title_full | Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells |
title_fullStr | Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells |
title_full_unstemmed | Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells |
title_short | Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells |
title_sort | chemically modified oligonucleotides modulate an epigenetically varied and transient form of transcription silencing of hiv-1 in human cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381641/ https://www.ncbi.nlm.nih.gov/pubmed/23343927 http://dx.doi.org/10.1038/mtna.2012.8 |
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