Transcription elongation and eukaryotic gene regulation.
Each step in the synthesis of functional transcript by RNA polymerase II provides a level at which gene expression can be regulated. Control over the elongation phase of transcription is a recognized regulatory mechanism in prokaryotes; however, only recently have examples of conditional transcription elongation blockage been reported in eukaryotic cellular genes. In several cases, control over transcription elongation clearly contributes to the regulated expression of these genes. Indeed, reports that transcription by RNA polymerase II is initiated and paused on many Drosophila promoters, prior to induction of gene expression, suggests that release of an arrested polymerase, as opposed to polymerase recruitment to a disengaged promoter, may be the key regulatory step for many genes thought to be controlled by transcription initiation (Rougvie & Lis, 1988). RNA polymerase II undergoes modifications, such as association with ancillary elongation factors and phosphorylation of its large subunit carboxy terminal domain (CTD), at stages subsequent to recruitment to a promoter and establishment of a pre-initiation complex (Reinberg & Roeder, 1987; Rappaport et al., 1987; Payne et al., 1989; Laybourn & Dahmus, 1989). It is possible that modifications such as these, or others occurring prior to, during or following transcription initiation, may alter the holoenzyme's transcription elongation properties, to allow recognition or read-through of elongation block signals within a transcription unit. In this review, we will present features of transcription elongation blockage in several eukaryotic cellular genes in the context of our understanding of attenuation and premature transcription termination in prokaryotic and viral genes. We will also present evidence supporting the model that modifications to the RNA polymerase II transcription complex are pivotal to the control of transcriptional at the level of elongation.
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
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Spencer
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Groudine
D000818:Animals; D002468:Cell Physiological Phenomena; D005057:Eukaryotic Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*