In mammalian mitochondria, mRNAs are cotranscriptionally stabilized by the protein factor LRPPRC (leucine-rich pentatricopeptide repeat-containing protein). Here, we characterize LRPPRC as an mRNA delivery factor and report its cryo-electron microscopy structure in complex with SLIRP (SRA stem-loop-interacting RNA-binding protein), mRNA and the mitoribosome. The structure shows that LRPPRC associates with the mitoribosomal proteins mS39 and the N terminus of mS31 through recognition of the LRPPRC helical repeats. Together, the proteins form a corridor for handoff of the mRNA. The mRNA is directly bound to SLIRP, which also has a stabilizing function for LRPPRC. To delineate the effect of LRPPRC on individual mitochondrial transcripts, we used RNA sequencing, metabolic labeling and mitoribosome profiling, which showed a transcript-specific influence on mRNA translation efficiency, with cyclooxygenase 1 and 2 translation being the most affected. Our data suggest that LRPPRC–SLIRP acts in recruitment of mitochondrial mRNAs to modulate their translation. Collectively, the data define LRPPRC–SLIRP as a regulator of the mitochondrial gene expression system.

在哺乳动物线粒体中，mRNA 被蛋白质因子 LRPPRC （富含亮氨酸的五肽重复序列包含的蛋白质） 共转录稳定。在这里，我们将 LRPPRC 表征为 mRNA 递送因子，并报告其与 SLIRP （SRA 茎环相互作用 RNA 结合蛋白）、mRNA 和线粒体核糖体的复合物中的冷冻电子显微镜结构。该结构表明，LRPPRC 通过识别 LRPPRC 螺旋重复序列与线粒体蛋白 mS39 和 mS31 的 N 末端结合。这些蛋白质一起形成了一条 mRNA 传递的走廊。mRNA 直接与 SLIRP 结合，SLIRP 对 LRPPRC 也具有稳定功能。为了描述 LRPPRC 对单个线粒体转录本的影响，我们使用了 RNA 测序、代谢标记和线粒体核糖体分析，这显示了转录本对 mRNA 翻译效率的特异性影响，其中环氧合酶 1 和 2 翻译受影响最大。我们的数据表明，LRPPRC-SLIRP 在线粒体 mRNA 的募集中发挥作用以调节其翻译。总的来说，数据将 LRPPRC-SLIRP 定义为线粒体基因表达系统的调节因子。