SURVEY AND SUMMARY Spatial organization of transcription by RNA polymerase III

RNA polymerase III (pol III) transcribes many essential, small, noncoding RNAs, including the 5S rRNAs and tRNAs. While most pol III-transcribed genes are found scattered throughout the linear chromosome maps or in multiple linear clusters, there is increasing evidence that many of these genes prefer to be spatially clustered, often at or near the nucleolus. This association could create an environment that fosters the coregulation of transcription by pol III with transcription of the large ribosomal RNA repeats by RNA polymerase I (pol I) within the nucleolus. Given the high number of pol III-transcribed genes in all eukaryotic genomes, the spatial organization of these genes is likely to affect a large portion of the other genes in a genome. In this Survey and Summary we analyze the reports regarding the spatial organization of pol III genes and address the potential influence of this organization on transcriptional regulation. LINEAR GROUPINGS OF CO-REGULATED GENES The organization of coregulated genes is commonly found in the single dimension of a linear chromosome and the advantages for co-regulation of expression are obvious. This type of linear association is evidenced by gene clusters that are found in all three domains of life (1). In bacterial operons, coding regions for multiple genes are synthesized as a single transcript from a common promoter. The classic example is the bacterial lac operon, which includes the lacZYA genes under one promoter, in close proximity to the adjacent lacI regulatory gene under its own separate promoter. The direct association of this set of multiple genes, with multiple promoters, implies the utility of having related genes exist in the same subcellular environment. Archaeal genomes also exhibit this type of linear organization, such as a heat shock regulon that is found in all sequenced archaeal genomes (2). Operons are now known to exist widely in Caenorhabditis elegans, making up a surprising 15% of the genome (3). Most of these operons are conserved in Caenorhabditis briggsae and some are found in more distant nematodes (3). Other interesting examples of clustered linear gene arrangements can be found in metazoans, including the HOX gene clusters, which encode multiple transcription factors that pattern embryonic development along the anterior–posterior axis. The order of the genes in these clusters demonstrates a remarkable linear correlation to the actual location of gene expression in the animal, which suggests an intriguing method of coordinating gene position and expression. The human b-globin locus on chromosome 11 is another example of linear gene organization, with the epsilon, gamma, delta and beta genes arrayed 50–30 in the order in which they are developmentally expressed. RIBOSOMAL DNA IS ORGANIZED LINEARLY AND SPATIALLY Across all forms of life, the one gene family that is almost always found as an operon, typically in multiple copies, is that of the ribosomal DNA (rDNA). In prokaryotes the rDNA operon contains combinations of 16S, 23S and 5S genes, which are usually co-transcribed and then processed into individual RNAs by a series of endo-and exonucleolytic events in concert with assembly with protein subunits. In certain species, such as Chlamydia pneumoniae and Mycobacterium tuberculosis, the operon is found in only one copy (4). Other genomes contain multiple rDNA operons that are clustered at multiple sites on the chromosome, as seen in Escherichia coli and Bacillus subtilis (4). In eukaryotes, the rDNA operon includes the genes encoding 18S, 5.8S and 28S subunits, which are transcribed by RNA polymerase I (pol I). This operon is usually found in numerous tandem repeats: 150 in Saccharomyces cerevisiae, 400 in human and many thousands in various plant species (5). rDNA repeats are usually found in linear clusters at multiple chromosomal sites, although some species like S.cerevisiae have only one rDNA locus (5). This co-transcription of RNAs that are later processed into individual, functional *To whom correspondence should be addressed. Tel: +1 734 763 0641; Fax:+1 734 763 7799; Email: [email protected]