MPP6 is an exosome-associated RNA-binding protein involved in 5.8S rRNA maturation.

MPP6 is an exosome-associated RNA-binding protein involved in 5.8S rRNA maturation.
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DOI:
10.1093/nar/gki982
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发表时间:
2005
影响因子:
14.9
通讯作者:
Pruijn GJ
Pruijn GJ
中科院分区:
生物学2区
文献类型:
--
作者:
Schilders G;Raijmakers R;Raats JM;Pruijn GJ

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外泌体是一种由3′→5′核糖核酸外切酶组成的复合体,参与多种RNA代谢过程。为了调节这些功能,不同的蛋白质被认为将外泌体募集到特定的底物RNA。在这里,我们证明了M-相磷蛋白6(MPP 6),一种以前报道的与TAP标记的人外泌体共纯化的蛋白质,积累在HEp-2细胞的核仁中,并与核外泌体的一个子集相关联,如通过免疫共沉淀和生化分级实验所证明的。与其核仁积累一致,siRNA介导的敲除实验显示MPP 6参与5.8S rRNA 3′端的产生。在降低MPP 6或外泌体组分的水平后,相同的加工中间体的积累强烈表明,MPP 6是外泌体向pre-rRNA募集所必需的。有趣的是,MPP 6似乎在体外显示出RNA结合活性,偏好富含嘧啶的序列,并结合前体rRNA的ITS 2元件。我们的数据表明,MPP 6是一个核仁特异性的外泌体辅因子,其在5.8S rRNA成熟中的作用是必需的。
The exosome is a complex of 3′→5′ exoribonucleases which is involved in many RNA metabolic processes. To regulate these functions distinct proteins are believed to recruit the exosome to specific substrate RNAs. Here, we demonstrate that M-phase phosphoprotein 6 (MPP6), a protein reported previously to co-purify with the TAP-tagged human exosome, accumulates in the nucleoli of HEp-2 cells and associates with a subset of nuclear exosomes as evidenced by co-immunoprecipitation and biochemical fractionation experiments. In agreement with its nucleolar accumulation, siRNA-mediated knock-down experiments revealed that MPP6 is involved in the generation of the 3′ end of the 5.8S rRNA. The accumulation of the same processing intermediates after reducing the levels of either MPP6 or exosome components strongly suggests that MPP6 is required for the recruitment of the exosome to the pre-rRNA. Interestingly, MPP6 appeared to display RNA-binding activity in vitro with a preference for pyrimidine-rich sequences, and to bind to the ITS2 element of pre-rRNAs. Our data indicate that MPP6 is a nucleolus-specific exosome co-factor required for its role in the maturation of 5.8S rRNA.
DOI: 10.1084/jem.176.4.973
发表时间: 1992-10-01
期刊: The Journal of experimental medicine
影响因子: --
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发表时间: 2004-07-01
期刊: GENOME RESEARCH
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