Prieto José-Luis, McStay Brian
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY Scotland, United Kingdom.
Genes Dev. 2007 Aug 15;21(16):2041-54. doi: 10.1101/gad.436707.
Efficient ribosome biogenesis requires coordination of a highly complex series of events. Early events include pre-RNA transcription, processing, and modification. Analysis in yeast has demonstrated that t-UTPs, components of the U3 snoRNA-containing pre-rRNA processing complex, are required for efficient transcription of ribosomal genes (rDNA) by RNA polymerase I (pol I). Here, we characterize human t-UTPs and establish that their ability to link transcription and pre-rRNA processing is evolutionarily conserved. The pol I transcription factor UBF binds extensively across rDNA throughout the cell cycle, resulting in a specialized form of chromatin that is the hallmark of active nucleolar organizer regions (NORs). Transcriptionally silent pseudo-NORs are ectopic, chromosomally integrated, artificial arrays that mimic this specialized chromatin structure. Pseudo-NORs sequester t-UTPs and factors linking transcription with pre-rRNA modification (Nopp140 and Treacle). Recruitment is independent of transcription, the underlying DNA sequence, and location within the nucleolus. Previously, we have demonstrated that pseudo-NORs sequester every component of the pol I transcription machinery. Taken together, these results highlight the importance of the specialized chromatin structure at active NORs in coordinating early events in ribosome biogenesis and nucleolar formation.
高效的核糖体生物合成需要一系列高度复杂事件的协调。早期事件包括前体RNA转录、加工和修饰。在酵母中的分析表明,含U3 snoRNA的前体rRNA加工复合体的组分t-UTP,是RNA聚合酶I(pol I)高效转录核糖体基因(rDNA)所必需的。在这里,我们对人类t-UTP进行了表征,并证实它们连接转录和前体rRNA加工的能力在进化上是保守的。pol I转录因子UBF在整个细胞周期中广泛结合rDNA,形成一种特殊形式的染色质,这是活跃核仁组织区(NOR)的标志。转录沉默的假NOR是异位的、染色体整合的人工阵列,模仿这种特殊的染色质结构。假NOR隔离t-UTP以及将转录与前体rRNA修饰联系起来的因子(Nopp140和Treacle)。招募独立于转录、潜在的DNA序列以及在核仁内的位置。此前,我们已经证明假NOR隔离了pol I转录机制的每个组分。综上所述,这些结果突出了活跃NOR处特殊染色质结构在协调核糖体生物合成和核仁形成早期事件中的重要性。