Transcription elongation by RNA polymerase II: mechanism of SII activation.
RNA chain elongation by RNA polymerase is a dynamic process. Techniques that allow the isolation of active elongation complexes have enabled investigators to describe individual steps in the polymerization of RNA chains. This article will describe recent studies of elongation by RNA polymerase II (pol II). At least four types of blockage to chain elongation can be overcome by elongation factor SII: (a) naturally occurring "arrest" sequences, (b) DNA-bound protein, (c) drugs bound in the DNA minor groove, and (d) chain-terminating substrates incorporated into the RNA chain. SII binds to RNA polymerase II and stimulates a ribonuclease activity that shortens nascent transcripts from their 3' ends. This RNA cleavage is required for chain elongation from some template positions. As a result, the pol II elongation complex can repeatedly shorten and reextend the nascent RNA chain in a process we refer to as cleavage-resynthesis. Hence, assembly of large RNAs does not necessarily proceed in a direct manner. The ability to shorten and reextend nascent RNAs means that a transcription impediment through which only half the enzyme molecules can proceed per encounter, can be overcome by 99% of the molecules after six iterations of cleavage-resynthesis. Surprisingly, the boundaries of the elongation complex do not move upstream after RNA cleavage. The physico-chemical alterations in the elongation complex that accompany RNA cleavage and permit renewed chain elongation are not yet understood.
Reines
D
D
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA.
Ghanouni
P
P
Gu
W
W
Mote
J
J
Powell
W
W
D000818:Animals; D000911:Antibodies, Monoclonal; D001921:Brain; D002417:Cattle; D002474:Cell-Free System; D004591:Electrophoresis, Polyacrylamide Gel; D005092:Exonucleases / Q000502:physiology*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008099:Liver; D051379:Mice; D012319:RNA Polymerase II / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins; D013950:Thymus Gland; D014157:Transcription Factors / Q000378:metabolism*; D035165:Transcription Factors, General; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D035165:Transcription Factors, General; D035602:Transcriptional Elongation Factors; C018648:transcription factor S-II; D012319:RNA Polymerase II; D005092:Exonucleases