Margeot Antoine, Blugeon Corinne, Sylvestre Julien, Vialette Stéphane, Jacq Claude, Corral-Debrinski Marisol
Laboratoire de Génétique Moléculaire, UMR CNRS 8541, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
EMBO J. 2002 Dec 16;21(24):6893-904. doi: 10.1093/emboj/cdf690.
We recently demonstrated that polysome-associated mRNAs that co-isolate with mitochondria encode a subset of mitochondrial proteins, and that the 3' UTRs of these transcripts are essential for their localization to the vicinity of the organelle. To address the question of the involvement of the mRNA targeting process in mitochondrial biogenesis, we studied the role of ATP2 3' UTR. An altered ATP2 allele in which the 3' UTR was replaced by the ADH1 3' UTR exhibits properties supporting the importance of mRNA localization to the vicinity of mitochondria: (i) the mutated strain presents a respiratory dysfunction; (ii) mitochondrial import of the protein translated from the altered gene is strongly reduced, even though the precursor is addressed to the organelle surface; (iii) systematic deletions of ATP2 3' UTR revealed a 100 nucleotide element presenting RNA targeting properties. Additionally, when the ATM1 3' UTR was replaced by the ADH1 3' UTR, we obtained cells in which ATM1 mRNA is also delocalized, and presenting a respiratory dysfunction. This demonstrates that mRNA localization to the vicinity of mitochondria plays a critical role in organelle biogenesis.
我们最近证明,与线粒体共同分离的多聚核糖体相关mRNA编码线粒体蛋白的一个子集,并且这些转录本的3'UTR对于它们定位于细胞器附近至关重要。为了解决mRNA靶向过程参与线粒体生物发生的问题,我们研究了ATP2 3'UTR的作用。一个3'UTR被ADH1 3'UTR取代的ATP2等位基因变体表现出的特性支持了mRNA定位于线粒体附近的重要性:(i)突变菌株表现出呼吸功能障碍;(ii)从改变的基因翻译的蛋白质的线粒体导入显著减少,尽管前体被转运到细胞器表面;(iii)对ATP2 3'UTR的系统性缺失揭示了一个具有RNA靶向特性的100个核苷酸元件。此外,当ATM1 3'UTR被ADH1 3'UTR取代时,我们获得了其中ATM1 mRNA也发生定位错误且表现出呼吸功能障碍的细胞。这表明mRNA定位于线粒体附近在细胞器生物发生中起关键作用。