Importance of polyadenylation in the selective elimination of meiotic mRNAs in growing S. pombe cells.

Importance of polyadenylation in the selective elimination of meiotic mRNAs in growing S. pombe cells.
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DOI:
10.1038/emboj.2010.108
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发表时间:
2010-07-07
期刊:
The EMBO journal
影响因子:
--
通讯作者:
Yamamoto M
Yamamoto M
中科院分区:
其他
文献类型:
--
作者:
Yamanaka S;Yamashita A;Harigaya Y;Iwata R;Yamamoto M

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一些减数分裂特异性mrna最初是弱转录的,但随后在分裂酵母有丝分裂生长过程中被选择性地去除。这些mrna含有一个被称为DSR(选择性去除决定因素)的区域,该区域被YTH家族rna结合蛋白Mmi1p识别。Mmi1p与核外泌体协同指导这些mrna的破坏。然而,这种选择性mRNA消除过程的详细分子机制仍然难以捉摸。在这项研究中,我们证明了聚腺苷酸化在这一过程中的关键作用。双杂交和遗传筛选揭示了Mmi1p和参与聚腺苷酸化的蛋白之间潜在的相互作用。进一步的研究表明,外泌体破坏含有dsr的mrna需要典型聚(a)聚合酶的聚腺苷化。聚(a)结合蛋白Pab2p在聚(a)尾部的募集也是mRNA破坏的必要条件。在营养生长的细胞中,Mmi1p与外泌体、Pab2p和聚腺苷化复合体的组分一起定位在核质中的几个斑块结构中。这些斑块可能代表减数分裂特异性mrna不及时表达的降解位点。
A number of meiosis-specific mRNAs are initially weakly transcribed, but then selectively removed during fission yeast mitotic growth. These mRNAs harbour a region termed DSR (determinant of selective removal), which is recognized by the YTH family RNA-binding protein Mmi1p. Mmi1p directs the destruction of these mRNAs in collaboration with nuclear exosomes. However, detailed molecular mechanisms underlying this process of selective mRNA elimination have remained elusive. In this study, we demonstrate the critical role of polyadenylation in this process. Two-hybrid and genetic screens revealed potential interactions between Mmi1p and proteins involved in polyadenylation. Additional investigations showed that destruction of DSR-containing mRNAs by exosomes required polyadenylation by a canonical poly(A) polymerase. The recruitment of Pab2p, a poly(A)-binding protein, to the poly(A) tail was also necessary for mRNA destruction. In cells undergoing vegetative growth, Mmi1p localized with exosomes, Pab2p, and components of the polyadenylation complex in several patchy structures in the nucleoplasm. These patches may represent the sites for degradation of meiosis-specific mRNAs with untimely expression.
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