Crosstalk between mRNA 3' end processing and transcription initiation.
Transcription and mRNA maturation are interdependent events. Although stimulatory connections between these processes within the same round of transcription are well described, functional coupling between separate transcription cycles remains elusive. Comparing time-resolved transcription profiles of single-copy integrated β-globin gene variants, we demonstrate that a polyadenylation site mutation decreases transcription initiation of the same gene. Upon depletion of the 3' end processing and transcription termination factor PCF11, endogenous genes exhibit a similar phenotype. Readthrough RNA polymerase II (RNAPII) engaged on polyadenylation site-mutated transcription units sequester the transcription initiation/elongation factors TBP, TFIIB and CDK9, leading to their depletion at the promoter. Additionally, high levels of TBP and TFIIB appear inside the gene body, and Ser2-phosphorylated RNAPII accumulates at the promoter. Our data demonstrate that 3' end formation stimulates transcription initiation and suggest that coordinated recycling of factors from a gene terminator back to the promoter is essential for sustaining continued transcription.
Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, Aarhus University, C.F. Møllers Allé 3, Building 1130, DK-8000 Aarhus, Denmark.
Christophe K
CK
Mapendano
Søren
S
Lykke-Andersen
Jørgen
J
Kjems
Edouard
E
Bertrand
Torben Heick
TH
Jensen
D001483:Base Sequence; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D010641:Phenotype; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics; D011061:Poly A / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D026721:RNA 3' End Processing / Q000235:genetics*; D012319:RNA Polymerase II / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D035181:TATA-Box Binding Protein / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism
C521949:Pcf11 protein, human; D012333:RNA, Messenger; D035181:TATA-Box Binding Protein; D039221:mRNA Cleavage and Polyadenylation Factors; D010768:Phosphoserine; D011061:Poly A; D042863:Cyclin-Dependent Kinase 9; D012319:RNA Polymerase II