Multiple interactions between RNA polymerase I, TIF-IA and TAFI subunits regulate preinitiation complex assembly at the ribosomal gene promoter

被引:80
作者
Yuan, XJ [1 ]
Zhao, J [1 ]
Zentgraf, H [1 ]
Hoffmann-Rohrer, U [1 ]
Grummt, I [1 ]
机构
[1] German Canc Res Ctr, Div Mol Biol Cell 2, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
关键词
D O I
10.1093/embo-reports/kvf212
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In mammals, growth-dependent regulation of rRNA synthesis is brought about by the transcription initiation factor TIF-IA. TIF-IA is associated with a fraction of the TBP-containing factor TIF-IB/SL1 and the initiation-competent form of RNA polymerase I (Pol I). We investigated the mechanisms that down-regulate cellular pre-rRNA synthesis and demonstrate that nutrient starvation, density arrest and protein synthesis inhibitors inactivate TIF-IA and impair the association of TIF-IA with Pol I. Moreover, we used a panel of TIF-IA deletion mutants to map the domains that mediate the interaction of TIF-IA with Pol I and TIF-IB/SL1. We found that amino acids 512-609 interact with two subunits of Pol I, RPA43 and PAF67, whereas a short, conserved motif (LARAK, amino acids 411-415) is required for the association of TIF-IA with TAF(I)95 and TAF(I)68. The results uncover an interphase for essential protein-protein interactions that facilitate Pol I preinitiation complex formation.
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页码:1082 / 1087
页数:6
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