The Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, UK.
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Italy.
FEBS J. 2021 Jan;288(2):437-451. doi: 10.1111/febs.15342. Epub 2020 May 11.
In mammalian mitochondria, messenger RNA is processed and matured from large primary transcripts in structures known as RNA granules. The identity of the factors and process transferring the matured mRNA to the mitoribosome for translation is unclear. Nascent mature transcripts are believed to associate initially with the small mitoribosomal subunit prior to recruitment of the large subunit to form the translationally active monosome. When the small subunit fails to assemble, however, the stability of mt-mRNA is only marginally affected, and under these conditions, the LRPPRC/SLIRP RNA-binding complex has been implicated in maintaining mt-mRNA stability. Here, we exploit the activity of a bacterial ribotoxin, VapC20, to show that in the absence of the large mitoribosomal subunit, mt-mRNA species are selectively lost. Further, if the small subunit is also depleted, the mt-mRNA levels are recovered. As a consequence of these data, we suggest a natural pathway for loading processed mt-mRNA onto the mitoribosome.
在哺乳动物的线粒体中，信使 RNA 是从称为 RNA 颗粒的结构中的大型初级转录物中加工和成熟的。将成熟的 mRNA 转移到线粒体核糖体进行翻译的因素和过程尚不清楚。新生的成熟转录本最初被认为与小的线粒体核糖体亚基结合，然后招募大亚基形成翻译活性的单体。然而，当小亚基未能组装时，mt-mRNA 的稳定性仅受到轻微影响，在这些条件下，LRPPRC/SLIRP RNA 结合复合物被牵连到维持 mt-mRNA 的稳定性中。在这里，我们利用细菌核糖核酸酶 VapC20 的活性来表明，在缺乏大亚基的情况下，mt-mRNA 物种会被选择性地丢失。此外，如果小亚基也被耗尽，mt-mRNA 的水平会恢复。由于这些数据，我们提出了一种将加工后的 mt-mRNA 加载到线粒体核糖体上的自然途径。
