Control of the timing of promoter escape and RNA catalysis by the transcription factor IIb fingertip.
Transcription factor IIB (TFIIB) recruits RNA polymerase II to promoters and inserts a finger domain into its active site, with unknown consequences. Here we show that that the tip of this finger is important for two transcription initiation functions. First, TFIIB acts as a catalytic cofactor for initial RNA bond formation. It does so via a pair of fingertip aspartates that can bind magnesium, placing TFIIB within a family of proteins that insert finger domains to alter the catalytic functions of RNA polymerase. Second, the TFIIB fingertip mediates the timing of the release of TFIIB that is associated with appropriate promoter escape. These initiation requirements may assist in RNA quality control by minimizing functional synthesis when RNA polymerase becomes inappropriately associated with the genome without having been recruited there by TFIIB.
Tran
Khiem
K
Department of Chemistry and Biochemistry and The Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
Gralla
Jay D
JD
D002384:Catalysis; D015894:Genome, Human / Q000502:physiology; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D012319:RNA Polymerase II / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D035581:Transcription Factor TFIIB / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D035581:Transcription Factor TFIIB; D012319:RNA Polymerase II