Rudra Dipayan, Mallick Jaideep, Zhao Yu, Warner Jonathan R
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Mol Cell Biol. 2007 Jul;27(13):4815-24. doi: 10.1128/MCB.02062-06. Epub 2007 Apr 23.
It has become clear that in Saccharomyces cerevisiae the transcription of ribosomal protein genes, which makes up a major proportion of the total transcription by RNA polymerase II, is controlled by the interaction of three transcription factors, Rap1, Fhl1, and Ifh1. Of these, only Rap1 binds directly to DNA and only Ifh1 is absent when transcription is repressed. We have examined further the nature of this interaction and find that Ifh1 is actually associated with at least two complexes. In addition to its association with Rap1 and Fhl1, Ifh1 forms a complex (CURI) with casein kinase 2 (CK2), Utp22, and Rrp7. Fhl1 is loosely associated with the CURI complex; its absence partially destabilizes the complex. The CK2 within the complex phosphorylates Ifh1 in vitro but no other members of the complex. Two major components of this complex, Utp22 and Rrp7, are essential participants in the processing of pre-rRNA. Depletion of either protein, but not of other proteins in the early processing steps, brings about a substantial increase in ribosomal protein mRNA. We propose a model in which the CURI complex is a key mediator between the two parallel pathways necessary for ribosome synthesis: the transcription and processing of pre-rRNA and the transcription of ribosomal protein genes.
现已明确,在酿酒酵母中,核糖体蛋白基因的转录占RNA聚合酶II总转录量的很大一部分,其受三种转录因子Rap1、Fhl1和Ifh1的相互作用控制。其中,只有Rap1直接与DNA结合,且只有在转录受抑制时Ifh1才不存在。我们进一步研究了这种相互作用的性质,发现Ifh1实际上与至少两种复合物相关。除了与Rap1和Fhl1结合外,Ifh1还与酪蛋白激酶2(CK2)、Utp22和Rrp7形成一种复合物(CURI)。Fhl1与CURI复合物松散结合;它的缺失会部分破坏该复合物的稳定性。复合物中的CK2在体外使Ifh1磷酸化,但不使复合物中的其他成员磷酸化。该复合物的两个主要成分Utp22和Rrp7是前体rRNA加工过程中的必需参与者。耗尽这两种蛋白质中的任何一种,但不是早期加工步骤中的其他蛋白质,会导致核糖体蛋白mRNA大幅增加。我们提出了一个模型,其中CURI复合物是核糖体合成所需的两条平行途径之间的关键介质:前体rRNA的转录和加工以及核糖体蛋白基因的转录。