3′-end formation signals modulate the association of genes with the nuclear periphery as well as mRNP dot formation

3′-end formation signals modulate the association of genes with the nuclear periphery as well as mRNP dot formation
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DOI:
10.1038/sj.emboj.7601305
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发表时间:
2006-09-20
期刊:
影响因子:
11.4
通讯作者:
Rosbash, Michael
Rosbash, Michael
中科院分区:
生物学1区
文献类型:
--
作者:
Abruzzi, Katharine C.;Belostotsky, Dmitry A.;Rosbash, Michael

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多项研究表明,mRNA加工缺陷导致mRNAs在哺乳动物细胞和酵母中积累在离散的核焦点或点中。为了研究这一现象,我们研究了一系列整合到酵母基因组中与TetR-GFP结合的Teto位点阵列相邻的GAL报告结构。斑点内的mRNA主要是转录后的,斑点与其转录位点相邻,但与其转录位点不同。这些报告基因在基因诱导后也定位于核周,就像它们的内源性GAL对应基因一样。令人惊讶的是,这种外围定位在转录关闭后持续很长时间,并且在点中有类似的RNA持续。此外,在转录关闭后,点消失和基因从核外移以类似的动力学发生。这两种动力学依次依赖于报告基因3‘端的形成信号。我们的实验表明,基因与核外周的结合不需要进行转录,并表明斑点内的mRNPs可能对基因-核外周系链做出了主要贡献。
Multiple studies indicate that mRNA processing defects cause mRNAs to accumulate in discrete nuclear foci or dots, in mammalian cells as well as yeast. To investigate this phenomenon, we have studied a series of GAL reporter constructs integrated into the yeast genome adjacent to an array of TetR-GFP-bound TetO sites. mRNA within dots is predominantly post-transcriptional, and dots are adjacent to but distinct from their transcription site. These reporter genes also localize to the nuclear periphery upon gene induction, like their endogenous GAL counterparts. Surprisingly, this peripheral localization persists long after transcriptional shutoff, and there is a comparable persistence of the RNA in the dots. Moreover, dot disappearance and gene delocalization from the nuclear periphery occur with similar kinetics after transcriptional shutoff. Both kinetics depend in turn on reporter gene 3'-end formation signals. Our experiments indicate that gene association with the nuclear periphery does not require ongoing transcription and suggest that the mRNPs within dots may make a major contribution to the gene-nuclear periphery tether.