title: Small RNA-induced transcriptional gene regulation in mammals mechanisms, therapeutic applications, and scope within the genome.
abstract: Argonaute-bound small RNAs, derived from RNA interference and related pathways, are well-known effectors of posttranscriptional gene silencing (PTGS). Yet, these complexes also play an important role in affecting gene expression at the transcriptional level, either by transcriptional gene silencing (TGS) or activation (TGA). Our current understanding of how small RNAs are able to both activate and suppress transcription is unclear. In this review, we briefly outline the biogenesis of small RNAs and explore the mechanisms behind the various phenomena attributed to AGO-bound small RNA-mediated transcriptional regulation. The therapeutic potential of TGS and TGA is examined, emphasizing the distinct advantages over PTGS approaches with examples of application to cancer and diseases associated with viruses, aberrant splicing, and dysregulated heterochromatin. Finally, the influence of promoter architecture on gene susceptibility to transcriptional regulation is discussed in the light of how this impacts the scope of small RNA-induced transcriptional regulation within the genome.
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Green
authors.forename: Marc S
authors.initials: MS
authors.lastname: Weinberg
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D020868:Gene Silencing; D016678:Genome / Q000235:genetics*; D008322:Mammals / Q000235:genetics*; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000627:therapeutic use*; D014158:Transcription, Genetic
chemical_list: D034741:RNA, Small Interfering