Divergent contributions of conserved active site residues to transcription by eukaryotic RNA polymerases I and II.
Divergent contributions of conserved active site residues to transcription by eukaryotic RNA polymerases I and II.
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DOI:
10.1016/j.celrep.2013.07.044
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发表时间:
2013-09-12
期刊:
影响因子:
8.8
通讯作者:
Schneider DA
中科院分区:
文献类型:
--
作者:
Viktorovskaya OV;Engel KL;French SL;Cui P;Vandeventer PJ;Pavlovic EM;Beyer AL;Kaplan CD;Schneider DA
Multisubunit RNA polymerases (msRNAPs) exhibit high sequence and structural homology, especially within their active sites, which is generally thought to result in msRNAP functional conservation. However, we show that mutations in the trigger loop (TL) in the largest subunit of RNA polymerase I (Pol I) yield phenotypes unexpected from studies of Pol II. For example, a well-characterized gain-of-function mutation in Pol II results in loss-of-function in Pol I [Pol II: rpb1- E1103G; Pol I: rpa190-E1224G]. Studies of chimeric Pol II enzymes hosting Pol I or Pol III TLs suggest that consequences of mutations that alter TL dynamics are dictated by the greater enzymatic context and not solely the TL sequence. Although the rpa190-E1224G mutation diminishes polymerase function, when combined with mutations that perturb Pol I catalysis, it enhances polymerase function, similar to the analogous Pol II mutation. These results suggest that Pol I and Pol II have different rate-limiting steps.
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