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An algorithm for generating small RNAs capable of epigenetically modulating transcriptional gene silencing and activation in human cells

Abstract

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.

Type Journal
Authors Ackley, A.; Lenox, A.; Stapleton, K.; Knowling, S.; Lu, T.; Sabir, K. S.; Vogt P. K. ; Morris, K. V.
Garvan Authors Kenneth Sabir
Publisher Name MOL THER
Published Date 2013-07-09 00:00:00
Published Volume 2
Published Pages e104
URL http://www.ncbi.nlm.nih.gov/pubmed/23839098
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?11819_12500/13_Ackley_MolTher_.pdf