Co-transcriptional gene silencing (CTGS)

By the term CTGS (co-transcriptional gene silencing) we refer to mechanisms that degrade RNA in association with chromatin. Our work in S. pombe revealed that RNAi as well as other nuclear RNA degradation pathways mediate CTGS (see also 2.). While initially proposed to be important for the tight repression of heterochromatin, our recent work showed that the concept of CTGS also applies to euchromatin.

RNAi in S. pombe is well known for its critical role in the formation of heterochromatin and silencing thereof by degrading heterochromatic transcripts on a co-transcriptional level (CTGS). It has remained unclear, however, whether RNAi also functions outside constitutive heterochromatin. Using DNA adenine methyltransferase identification (DamID), we discovered that RNAi proteins physically associate with some euchromatic genes, noncoding RNA genes, and retrotransposon long terminal repeats. This physical association of RNAi with chromatin is sufficient to trigger a silencing response but not to assemble heterochromatin. The mode of silencing at the newly identified RNAi targets is consistent with our CTGS model and functions with trace amounts of siRNAs. Thus, RNAi-mediated degradation of RNA in association with chromatin turns out to be more prevalent than expected.

Whether RNAi regulates the expression of protein-coding genes in S. pombe has remained elusive for a long time. As novel physiological targets of RNAi, we identified a class of genes which are bound by the stress response transcription factor Atf1 and which we refer to as BANCs. We found that BANC genes are associated with nuclear pore complexes (NPCs) and RNAi proteins, which are all required for their tight repression. Because RNA polymerase II occupancy is not affected in RNAi mutants at the majority of BANCs, we conclude that RNAi functions on a truly co-transcriptional level to tightly repress this class of genes under non-stressful conditions (see also 4.).

 

Original publication:

Woolcock et al, G&D, 2012

Woolcock et al, NSMB, 2011

Bühler et al, Cell, 2007

Bühler et al, Cell, 2006

 

Further reading:

Collins K: 2011. F1000.com/7989964#eval8370064

Bayne, White and Allshire, Cell. 2007; 129(4): 651-653

Asher Mullard, Nature Reviews Molecular Cell Biology. 2007; 8: 513

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