TIBS 16 - NOVEMBER 1991
RNA POLYMERASE III OR C (pol Ill) transcribes a limited set of small genes in eukaryotes. Its main products are 5S RNA and tRNA but some small nuclear and viral RNA ," "es are also transcribed. Detailee analysis of the transcription components and promoter control regions of these genes has revealed an unexpected complexity at the protein level that matches a great diversity of promoter organization, with intragenic and/or extragenic elements. Since the last comprehensive reviews on transcription of pol III genes ],z, progress has been made in characterizing the protein components of the transcription complexes and in their function in complex assembly and polymerase selection. The emerging picture is that genes transcribed by pol III use, in original ways, many of the same general strategies for transcription complex formation and occasionally the same components as the genes transcribed by pol II.
Promoter diversity The study of the promoter organization of class III genes has been a history of surprises. (Class III genes are those transcribed by pol III, class II genes are those transcribed by pol II, and so on.) First, Xenopus laevis 5S RNA genes and later tRNA genes were found to have their control regions localized entirely in the transcribed region (for review see Ref. I); there was then the opposite finding that the class III vertebrate U6 and human 7SK genes use class II promoter elements, which were found entirely in upstream sequences (for review see Ref. 2); finally, and more recently, some class III genes were found to combine elements from these two promoter classes, suggesting that intragenic and extragenic promoters were not as distinct from each other as was at first thought. Intragenic promoters are found in the majority of genes encociing tRNA and 5S RNA as well as in the 7SL gene and in the VA, EBER and Alu gene families ~. The 5S RNA genes contain an 'A box'promoter element associated with an 'intermediate domain' and a 'C box', all
o. s. Gabdelsenand A. Sentenacare at the Service de Biochimieet G~n6tique Mol~culaire, Centred'Etudesde Saclay, 91191 Gif-sur-YvetteCedex,France.
412
Transcription of small genes by RNA polymerase III or C (pol III) involves many of the strategies that are used for transcription complex formation and occasionally the same components as those used by RNA polymerase II or B (pol II). Transcription complex formation is a multistep process that leads to the binding of a single initiation factor, TRIIB, which in turn directs the selection of pol II1. The general transcription factor TFIID can be involved in both pol II and pol III transcription. These and other similarities point towards a unifying mechanism for eukaryotic transcription initiation. of which are in rather fixed relative positions in the transcribed region. The tRNA genes are under the control of an intragenic A box and B box, where the B box functions at a variable distance. The 5' flanking sequence may modulate the efficiency of transcription significantly, either in a positive or negative sense; however no specific sequence element has yet been identified. Extrogenic promoters. A typical class III extragenic promoter, with all promoter elements localized upstream of the transcribed sequence, is found in genes such as those encoding small nuclear vertebrate U6 RNA (snRNA) and human 7SK RNA. The whole transcribed sequence, including a potential A box, can be removed with no effect on transcription efficiency. Three promoter elements have been identified~-. A TATA motif is essential for transcription both in vitro and in vivo. It is similar in sequence and position to the TATA box found in mRNA-encoding genes, and both motifs are functionally interchangeable 2-4. The intriguing observation was that in a U6 gene, a typical pol II promoter element such as the TATA motif was the major determinant for pol III specificity. A proximal sequence element (PSE) is found in similar but not identical positions in pol II and pol III genes around -602,s. A distal sequence element (DSE, around -250) is an enhancer-like element shared by class II snRNA genes and several external class III promoters. Mixed promoters. The Xenopus laevis selenocysteine tRNA
RNA POLYMERASE III OR C (pol Ill) transcribes a limited set of small genes in eukaryotes. Its main products are 5S RNA and tRNA but some small nuclear and viral RNA ," "es are also transcribed. Detailee analysis of the transcription components and promoter control regions of these genes has revealed an unexpected complexity at the protein level that matches a great diversity of promoter organization, with intragenic and/or extragenic elements. Since the last comprehensive reviews on transcription of pol III genes ],z, progress has been made in characterizing the protein components of the transcription complexes and in their function in complex assembly and polymerase selection. The emerging picture is that genes transcribed by pol III use, in original ways, many of the same general strategies for transcription complex formation and occasionally the same components as the genes transcribed by pol II.
Promoter diversity The study of the promoter organization of class III genes has been a history of surprises. (Class III genes are those transcribed by pol III, class II genes are those transcribed by pol II, and so on.) First, Xenopus laevis 5S RNA genes and later tRNA genes were found to have their control regions localized entirely in the transcribed region (for review see Ref. I); there was then the opposite finding that the class III vertebrate U6 and human 7SK genes use class II promoter elements, which were found entirely in upstream sequences (for review see Ref. 2); finally, and more recently, some class III genes were found to combine elements from these two promoter classes, suggesting that intragenic and extragenic promoters were not as distinct from each other as was at first thought. Intragenic promoters are found in the majority of genes encociing tRNA and 5S RNA as well as in the 7SL gene and in the VA, EBER and Alu gene families ~. The 5S RNA genes contain an 'A box'promoter element associated with an 'intermediate domain' and a 'C box', all
o. s. Gabdelsenand A. Sentenacare at the Service de Biochimieet G~n6tique Mol~culaire, Centred'Etudesde Saclay, 91191 Gif-sur-YvetteCedex,France.
412
Transcription of small genes by RNA polymerase III or C (pol III) involves many of the strategies that are used for transcription complex formation and occasionally the same components as those used by RNA polymerase II or B (pol II). Transcription complex formation is a multistep process that leads to the binding of a single initiation factor, TRIIB, which in turn directs the selection of pol II1. The general transcription factor TFIID can be involved in both pol II and pol III transcription. These and other similarities point towards a unifying mechanism for eukaryotic transcription initiation. of which are in rather fixed relative positions in the transcribed region. The tRNA genes are under the control of an intragenic A box and B box, where the B box functions at a variable distance. The 5' flanking sequence may modulate the efficiency of transcription significantly, either in a positive or negative sense; however no specific sequence element has yet been identified. Extrogenic promoters. A typical class III extragenic promoter, with all promoter elements localized upstream of the transcribed sequence, is found in genes such as those encoding small nuclear vertebrate U6 RNA (snRNA) and human 7SK RNA. The whole transcribed sequence, including a potential A box, can be removed with no effect on transcription efficiency. Three promoter elements have been identified~-. A TATA motif is essential for transcription both in vitro and in vivo. It is similar in sequence and position to the TATA box found in mRNA-encoding genes, and both motifs are functionally interchangeable 2-4. The intriguing observation was that in a U6 gene, a typical pol II promoter element such as the TATA motif was the major determinant for pol III specificity. A proximal sequence element (PSE) is found in similar but not identical positions in pol II and pol III genes around -602,s. A distal sequence element (DSE, around -250) is an enhancer-like element shared by class II snRNA genes and several external class III promoters. Mixed promoters. The Xenopus laevis selenocysteine tRNA
