The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts.
The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts.
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DOI：
10.1016/j.celrep.2018.04.061
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发表时间：
2018-05-15
期刊：
影响因子：
8.8
通讯作者：
Jensen TH
中科院分区：
文献类型：
--
作者：
Silla T;Karadoulama E;Mąkosa D;Lubas M;Jensen TH
哺乳动物基因组混杂转录，产生蛋白质编码和非编码产物。许多转录本由于它们被核糖核溶解RNA外泌体的核降解而寿命很短。在这里，我们表明，废除核外泌体功能的原因形成不同的核病灶，含有多聚腺苷酸化（PA+）RNA隔离从核质出口。我们询问外泌体辅因子是否可以服务于这种核保留。共定位研究揭示了具有“PA-尾外来体靶向（PAXT）连接”组分MTR 4、ZFC 3 H1和PABPN 1的PA+ RNA焦点的富集，但与已知的核结构如卡哈尔体、斑点、旁斑点或核仁没有重叠。有趣的是，ZFC 3 H1是病灶形成所需的，在其缺失的情况下，选择的pA+ RNA，包括编码和非编码转录本，在依赖于mRNA输出因子AlyREF的过程中被输出到细胞质。我们的研究结果建立ZFC 3 H1作为一个中央核PA+ RNA保留因子，抵消核输出活动。缺失的RNA外泌体功能导致核灶中的pA+ RNA积累。pA+ RNA灶富含各种转录物和外泌体衔接蛋白。外泌体衔接蛋白ZFC 3 H1是pA+ RNA灶形成所需的ZFC 3 H1在功能上抵消mRNA输出因子AlyREF Silla et al.报道RNA外泌体衔接蛋白ZFC 3 H1作为核RNA保留因子。在不存在ZFC 3 H1的情况下，外泌体靶标以AlyREF依赖性方式输出至细胞质。这一发现确立了ZFC 3 H1作为多聚腺苷酸化RNA保留和降解的中心因子。
Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci, containing polyadenylated (pA+) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA+ RNA foci with “pA-tail exosome targeting (PAXT) connection” components MTR4, ZFC3H1, and PABPN1 but no overlap with known nuclear structures such as Cajal bodies, speckles, paraspeckles, or nucleoli. Interestingly, ZFC3H1 is required for foci formation, and in its absence, selected pA+ RNAs, including coding and non-coding transcripts, are exported to the cytoplasm in a process dependent on the mRNA export factor AlyREF. Our results establish ZFC3H1 as a central nuclear pA+ RNA retention factor, counteracting nuclear export activity. Abolished RNA exosome function leads to pA+ RNA accumulation in nuclear foci pA+ RNA foci are enriched with various transcripts and exosome adaptor proteins The exosome adaptor protein ZFC3H1 is required for pA+ RNA foci formation ZFC3H1 functionally counteracts the mRNA export factor AlyREF Silla et al. report that the RNA exosome adaptor protein ZFC3H1 acts as a nuclear RNA retention factor. In the absence of ZFC3H1, exosome targets are exported to the cytoplasm in a AlyREF-dependent manner. The discovery establishes ZFC3H1 as a central factor in the retention and degradation of polyadenylated RNA.
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