The exosome and heterochromatin: multilevel regulation of gene silencing.

Heterochromatic silencing is important for repressing gene expression, protecting cells against viral invasion, maintaining DNA integrity and for proper chromosome segregation. Recently, it has become apparent that expression of eukaryotic genomes is far more complex than had previously been anticipated. Strikingly, it has emerged that most of the genome is transcribed including intergenic regions and heterochromatin, calling for us to re-address the question of how gene silencing is regulated and re-evaluate the concept of heterochromatic regions of the genome being transcriptionally inactive. Although heterochromatic silencing can be regulated at the transcriptional level, RNA degrading activities supplied either by the exosome complex or RNAi also significantly contribute to this process. The exosome also regulates noncoding RNAs (ncRNAs) involved in the establishment of heterochromatin, further underscoring its role as the major cellular machinery involved in RNA processing and turn-over. This multilevel control of the transcriptome may be utilized to ensure greater accuracy of gene expression and allow distinction between functional transcripts and background noise. In this chapter, we will discuss the regulation of gene silencing across species, with special emphasis on the exosome's contribution to the process. We will also discuss the links between transcriptional and posttranscriptional mechanisms for gene silencing and their impact on the regulation of eukaryotic transcriptomes.