Clausmeyer S, Stürzebecher R, Peters J
Department of Pharmacology, University of Heidelberg, Germany.
Circ Res. 1999 Feb 19;84(3):337-44. doi: 10.1161/01.res.84.3.337.
Characterization of the local renin-angiotensin system in the rat adrenal zona glomerulosa indicated a dual targeting of renin both to the secretory pathway and mitochondria. To investigate the transport of renin into mitochondria, we constructed a series of amino-terminal deletion variants of preprorenin. One of these variants, lacking the complete signal sequence for the endoplasmic reticulum and 10 amino acids of the profragment, was transported efficiently into isolated mitochondria. The transport was further shown to be dependent on mitochondrial membrane potential and ATP synthesis. Analysis of adrenal RNA revealed the existence of 2 renin transcripts. While one of the transcripts corresponds to the known full-length transcript, the other one lacks exon 1; instead, exon 2 is preceded by a domain of 80 nucleotides originating from intron 1. This domain, as well as the following region of intron 1 being excised, shows all essential sequence elements defining an additional, so-far-unknown exon. The second mRNA possibly derives from an additional transcription start in intron 1 and an alternative splicing process. Translation of this mRNA could result in a truncated prorenin representing a cytosolic form of renin, which is required for transport into mitochondria. This truncated prorenin corresponds exactly to the deletion variant being imported into mitochondria in vitro.
对大鼠肾上腺球状带局部肾素 - 血管紧张素系统的表征表明，肾素同时靶向分泌途径和线粒体。为了研究肾素向线粒体的转运，我们构建了一系列前肾素的氨基末端缺失变体。其中一个变体，缺少内质网的完整信号序列和前肽的10个氨基酸，能有效地转运到分离的线粒体中。进一步表明，这种转运依赖于线粒体膜电位和ATP合成。对肾上腺RNA的分析揭示了2种肾素转录本的存在。其中一种转录本对应于已知的全长转录本，而另一种缺少外显子1；相反，外显子2之前是一个源自内含子1的80个核苷酸的结构域。该结构域以及随后被切除的内含子1区域，显示出定义一个额外的、迄今未知的外显子的所有必需序列元件。第二种mRNA可能源自内含子1中的另一个转录起始位点和一个可变剪接过程。这种mRNA的翻译可能导致一种截短的前肾素，代表肾素的一种胞质形式，这是转运到线粒体所必需的。这种截短的前肾素与在体外导入线粒体的缺失变体完全对应。
