NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway.
NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway.
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NMD3通过XPOI连接的途径调节非洲锥虫中的mRNA和rRNA核输出。
DOI：
10.1093/nar/gkv330
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发表时间：
2015-05-19
影响因子：
14.9
通讯作者：
Matthews KR
中科院分区：
文献类型：
--
作者：
Bühlmann M;Walrad P;Rico E;Ivens A;Capewell P;Naguleswaran A;Roditi I;Matthews KR
锥虫主要通过转录后机制调控基因表达，尤其是mRNA的稳定性。然而，许多mRNA降解是细胞质的，因此mRNA核输出必须代表一个重要的调控水平。核糖体rna也必须从细胞核中输出，而锥虫的NMD3同源物已被证实参与rRNA的加工和输出，与其在其他生物中的功能相匹配。令人惊讶的是，我们发现TbNMD3的缺失也会产生原环素相关基因（PAGs）的mRNA积累，这些基因通过RNA聚合酶I与原环素表面抗原基因在锥虫昆虫上表达共转录。通过对TbNMD3缺失细胞的全转录组RNA-seq分析，我们证实了TbNMD3对PAG转录物的调控，并使用报告基因构建物揭示了PAG1的调控是由其5'UTR介导的。对调控机制的剖析表明，它不依赖于TbNMD3缺失介导的翻译抑制，也不依赖于转录增强。然而，核输出因子XPO1或MEX67的缺失概括了TbNMD3缺失对PAG mrna和TbNMD3缺失细胞细胞核中积累的mrna的影响。这些结果提出了一种新的RNA调控机制，涉及依赖nmd3的mRNA货物核输出，表明mRNA和rRNA输出存在共享平台。
Trypanosomes mostly regulate gene expression through post-transcriptional mechanisms, particularly mRNA stability. However, much mRNA degradation is cytoplasmic such that mRNA nuclear export must represent an important level of regulation. Ribosomal RNAs must also be exported from the nucleus and the trypanosome orthologue of NMD3 has been confirmed to be involved in rRNA processing and export, matching its function in other organisms. Surprisingly, we found that TbNMD3 depletion also generates mRNA accumulation of procyclin-associated genes (PAGs), these being co-transcribed by RNA polymerase I with the procyclin surface antigen genes expressed on trypanosome insect forms. By whole transcriptome RNA-seq analysis of TbNMD3-depleted cells we confirm the regulation of the PAG transcripts by TbNMD3 and using reporter constructs reveal that PAG1 regulation is mediated by its 5′UTR. Dissection of the mechanism of regulation demonstrates that it is not dependent upon translational inhibition mediated by TbNMD3 depletion nor enhanced transcription. However, depletion of the nuclear export factors XPO1 or MEX67 recapitulates the effects of TbNMD3 depletion on PAG mRNAs and mRNAs accumulated in the nucleus of TbNMD3-depleted cells. These results invoke a novel RNA regulatory mechanism involving the NMD3-dependent nuclear export of mRNA cargos, suggesting a shared platform for mRNA and rRNA export.
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影响因子：
14.8
作者：
Dahl, John Arne;Collas, Philippe
通讯作者：
Collas, Philippe
DOI：
10.1038/nrm3454
发表时间：
2012-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.6
作者：
Dostalova, Anna;Kaeser, Sandro;Schimanski, Bernd
通讯作者：
Schimanski, Bernd
影响因子：
1.5
作者：
Haenni, Simon;Renggli, Christina Kunz;Roditi, Isabel
通讯作者：
Roditi, Isabel
影响因子：
1.5
作者：
Burkard, Gabriela;Fragoso, Cristina M.;Roditi, Isabel
通讯作者：
Roditi, Isabel