An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells
Small noncoding antisense RNAs (sasRNAs) guide epigenetic silencing complexes to target loci in human cells and modulate gene transcription. When these targeted loci are situated within a promoter, long-term, stable epigenetic silencing of transcription can occur. Recent studies suggest that there e...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-01-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253116301652 |
| _version_ | 1818959275796463616 |
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| author | Amanda Ackley Alexandra Lenox Kenneth Stapleton Stuart Knowling Tim Lu Kenny S Sabir Peter K Vogt Kevin V Morris |
| author_facet | Amanda Ackley Alexandra Lenox Kenneth Stapleton Stuart Knowling Tim Lu Kenny S Sabir Peter K Vogt Kevin V Morris |
| author_sort | Amanda Ackley |
| collection | DOAJ |
| description | Small noncoding antisense RNAs (sasRNAs) guide epigenetic silencing complexes to target loci in human cells and modulate gene transcription. When these targeted loci are situated within a promoter, long-term, stable epigenetic silencing of transcription can occur. Recent studies suggest that there exists an endogenous form of such epigenetic regulation in human cells involving long noncoding RNAs. In this article, we present and validate an algorithm for the generation of highly effective sasRNAs that can mimic the endogenous noncoding RNAs involved in the epigenetic regulation of gene expression. We validate this algorithm by targeting several oncogenes including AKT-1, c-MYC, K-RAS, and H-RAS. We also target a long antisense RNA that mediates the epigenetic repression of the tumor suppressor gene DUSP6, silenced in pancreatic cancer. An algorithm that can efficiently design small noncoding RNAs for the epigenetic transcriptional silencing or activation of specific genes has potential therapeutic and experimental applications. |
| first_indexed | 2024-12-20T11:39:03Z |
| format | Article |
| id | doaj.art-20c51ae8a73c411c98bf011a2eeb55d1 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-20T11:39:03Z |
| publishDate | 2013-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-20c51ae8a73c411c98bf011a2eeb55d12022-12-21T19:42:02ZengElsevierMolecular Therapy: Nucleic Acids2162-25312013-01-012C10.1038/mtna.2013.33An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human CellsAmanda Ackley0Alexandra Lenox1Kenneth Stapleton2Stuart Knowling3Tim Lu4Kenny S Sabir5Peter K Vogt6Kevin V Morris7Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USADepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USADepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USADepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USADepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USAGarvan Institute of Medical Research, Sydney, AustraliaDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USADepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USASmall noncoding antisense RNAs (sasRNAs) guide epigenetic silencing complexes to target loci in human cells and modulate gene transcription. When these targeted loci are situated within a promoter, long-term, stable epigenetic silencing of transcription can occur. Recent studies suggest that there exists an endogenous form of such epigenetic regulation in human cells involving long noncoding RNAs. In this article, we present and validate an algorithm for the generation of highly effective sasRNAs that can mimic the endogenous noncoding RNAs involved in the epigenetic regulation of gene expression. We validate this algorithm by targeting several oncogenes including AKT-1, c-MYC, K-RAS, and H-RAS. We also target a long antisense RNA that mediates the epigenetic repression of the tumor suppressor gene DUSP6, silenced in pancreatic cancer. An algorithm that can efficiently design small noncoding RNAs for the epigenetic transcriptional silencing or activation of specific genes has potential therapeutic and experimental applications.http://www.sciencedirect.com/science/article/pii/S2162253116301652epigeneticnon-coding RNAoncogenetranscriptiontumor suppressor gene |
| spellingShingle | Amanda Ackley Alexandra Lenox Kenneth Stapleton Stuart Knowling Tim Lu Kenny S Sabir Peter K Vogt Kevin V Morris An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells Molecular Therapy: Nucleic Acids epigenetic non-coding RNA oncogene transcription tumor suppressor gene |
| title | An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells |
| title_full | An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells |
| title_fullStr | An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells |
| title_full_unstemmed | An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells |
| title_short | An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells |
| title_sort | algorithm for generating small rnas capable of epigenetically modulating transcriptional gene silencing and activation in human cells |
| topic | epigenetic non-coding RNA oncogene transcription tumor suppressor gene |
| url | http://www.sciencedirect.com/science/article/pii/S2162253116301652 |
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