ABSTRACT
Small RNAs regulate gene expression at the transcriptional and posttranscriptional levels through various RNA silencing pathways, including the well-characterized mechanism of RNA interference (RNAi). Classes of small RNAs include small interfering RNAs (siRNAs) and microRNAs (miRNAs), which associate with Argonaute (AGO) protein family members to mediate sequence-specific gene silencing of their targets. In mammalian cells, siRNAs that exhibit perfect Watson-Crick base pairing to gene promoters direct transcriptional gene silencing (TGS) through epigenetic modifications involving histone and/or DNA methylation events. While a role for miRNAs in TGS has not been explored, evidence in plants suggests that miRNAs may also play a role in directing heritable,
Overview ................................................................................................................ 393 20.1 Introduction .................................................................................................. 394 20.2 Classes of Small RNAs................................................................................. 394
20.2.1 Small Interfering RNAs.................................................................... 394 20.2.2 miRNAs ............................................................................................ 394
20.3 Transcriptional Gene Silencing .................................................................... 395 20.3.1 Gene Promoters ................................................................................ 395 20.3.2 DNA Methylation ............................................................................. 396 20.3.3 Histone Methylation.......................................................................... 397
20.4 Polycomb Group and RNAi Components .................................................... 398 20.4.1 Polycomb Group Silencing ............................................................... 398 20.4.2 Argonaute Proteins ........................................................................... 398
20.5 Therapeutic Applications of TGS .................................................................400 20.5.1 Cancer ...............................................................................................400 20.5.2 HIV ...................................................................................................402
20.6 Conclusions ...................................................................................................402 Acknowledgments ..................................................................................................402 References ..............................................................................................................402
