Small RNA-directed silencing mechanisms play important roles in the regulation of eukaryotic gene expression. In plants, insects, nematodes and fungi RNA silencing mechanisms are also involved in innate antiviral defence responses.

To counter antiviral RNA silencing, viruses from plants, insects and fungi encode RNA silencing suppressors (RSSs). Recent studies suggest that RNA silencing in mammals, or RNA interference (RNAi), is also involved in antiviral responses. In particular, there is increasing evidence that cellular regulatory microRNAs (miRNAs) have a function in restricting virus replication in mammalian cells. Similar to plant and insect viruses, several mammalian viruses encode RSS factors that inhibit the RNAi mechanism. Several of these suppressors are multifunctional proteins that were previously shown to block innate antiviral immune responses involving the interferon (IFN) pathway.

Further reading:

• RNA Interference and Viruses: Current Innovations and Future Trends
• RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity

Labels: MicroRNAs, miRNA, RNA silencing suppressors, RNAi, RSSs

Multicellular organisms have evolved sophisticated defense systems to confer protection against pathogens. An important characteristic of these immune systems is their ability to act both locally at the site of infection and at distal uninfected locations. Insects rely on multiple immune responses to combat infection; one of them is RNA interference (RNAi).

Further reading:

• RNA Interference and Viruses: Current Innovations and Future Trends
• RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity

Labels: RNA interference, RNAi

Epigenetics is the study of meiotically and mitotically heritable changes in gene expression which are not coded for in the DNA. Exactly how these epigenetic modifications are directed to the particular gene and the local chromatin has remained enigmatic. Three distinct mechanisms appear to be intricately related and implicated in initiating and/or sustaining epigenetic modifications; DNA methylation, RNA-associated silencing, and histone modifications.

In human cells RNA can specifically direct epigenetic modifications to targeted loci (the promoter regions) and modulate silencing. This regulatory effect is through RNA-associated silencing, can be transcriptional in nature, and is operable through an RNA interference based mechanism (RNAi) that is specifically mediated by the antisense strand of small-interfering RNAs (siRNAs). These recent observations represent a paradigm shift in which a hidden layer of complexity is involved in gene regualtion and is operative via the action RNA essentially epigenetically regulating DNA.

from Kevin V. Morris (2008). RNA Mediated Transcriptional Gene Silencing. In: Morris, K.V. (Ed.) RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Caister Academic Press, Norfolk, UK.

Further reading:

1. Epigenetics
2. RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity
3. Molecular Biology Books

Labels: epigenetics, expression, gene regulation, regulation, RNA, RNAi, siRNA

Short RNAs play multiple roles in affecting gene expression at many levels as illustrated by work in Drosophila. RNA interference uses double stranded RNA which is cleaved by Dicer to produce small interfering RNAs (siRNAs) as guides to cleave homologous mRNAs. This process occurs in the cytoplasm and is used in the endogenous process of viral resistance. In addition, many of the same gene products are also involved in transcriptional gene silencing processes. This was first documented for cosuppression of white-Alcohol dehydrogenase transgenes, which is associated with the Polycomb repressive complex of chromatin proteins. Genetic studies of RNA silencing genes also implicate a role in heterochromatin silencing. Some gene products involved in RNAi are also involved in the formation of repeat associated small RNAs (rasiRNAs), whose formation appears to be Dicer independent and critical for repressing transposon expression particularly in the germline. Roles for small RNAs are also implicated in chromatin insulator activity, the integrity of the nucleolus and long-range associations of homeotic genes.

from Kavi et al in RNA and the Regulation of Gene Expression

Labels: Drosophila, regulation, RNA, RNAi, siRNA

Heterochromatin is a prevalent chromatin state among eukaryotes that has critical functions in chromosome segregation, control of genomic stability and epigenetic regulation of gene expression. In the fission yeast Schizosaccharomyces pombe, two RNAi complexes, the RNAi-induced transcriptional gene silencing (RITS) complex and the RNA-directed RNA polymerase complex (RDRC), are part of a RNAi machinery involved in the initiation, propagation and maintenance of heterochromatin assembly. These two complexes localize in a siRNA-dependent manner on chromosomes, at the site of heterochromatin assembly. RNA polymerase II (RNApII) has a central role in RNAi-dependent heterochromatin assembly. RNApII synthesizes a nascent transcript that serves as an RNA platform to recruit RITS, RDRC and possibly other complexes required for heterochromatin assembly. Both RNAi and an exosome-dependent RNA degradation process contribute to heterochromatic gene silencing. Recently reported findings challenge the widely accepted view that heterochromatic gene silencing is caused strictly by chromatin compaction. As RNAi-dependent chromatin modifications have been observed throughout the eukaryotic kingdom the mechanisms described here may be utilized in a large range of eukaryotes.

from Vavasseur et al in RNA and the Regulation of Gene Expression

Further reading: Epigenetics

Labels: epigenetics, regulation, RNA, RNAi, siRNA, yeast

Regulation of gene expression is a complex, multi-layered process that is crucial to correctly drive and maintain cell identity during development and adult life. RNA interference (RNAi) and the Polycomb system are two well-conserved gene silencing pathways. RNAi participates in post transcriptional as well as transcriptional gene silencing of natural genes as well as transposons and viruses. Polycomb group (PcG) proteins are well-known for their role in silencing HOX genes through modulation of chromatin structure. Both mechanisms are involved in specific epigenetic processes like cosuppression in Drosophila melanogaster and the formation of C. elegans mes and SOP-2 complexes. There are molecular links between RNAi components and Polycomb-mediated silencing in human cells and in Drosophila. RNA polymerase II and Argonaute 1 interact to bring about chromatin modifications on endogenous Polycomb target gene promoters in human cells, while Drosophila RNAi components modulate the nuclear organization of PcG target DNA elements, thereby affecting the strength of PcG-mediated silencing. Several microRNAs and non coding RNAs have been found in human and fly HOX gene loci. They may regulate HOX gene expression both post-trascriptionally and co-transcriptionally.

from Portoso and Cavalli in RNA and the Regulation of Gene Expression (Chapter 3)

Labels: Drosophila, epigenetics, polycomb, regulation, RNA, RNAi