Department of Cellular Biochemistry, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
Research Group Structure and Function of Molecular Machines, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, 37077 Göttingen, Germany.
Hum Mol Genet. 2024 May 22;33(R1):R19-R25. doi: 10.1093/hmg/ddae023.
Human mitochondria harbour a circular, polyploid genome (mtDNA) encoding 11 messenger RNAs (mRNAs), two ribosomal RNAs (rRNAs) and 22 transfer RNAs (tRNAs). Mitochondrial transcription produces long, polycistronic transcripts that span almost the entire length of the genome, and hence contain all three types of RNAs. The primary transcripts then undergo a number of processing and maturation steps, which constitute key regulatory points of mitochondrial gene expression. The first step of mitochondrial RNA processing consists of the separation of primary transcripts into individual, functional RNA molecules and can occur by two distinct pathways. Both are carried out by dedicated molecular machineries that substantially differ from RNA processing enzymes found elsewhere. As a result, the underlying molecular mechanisms remain poorly understood. Over the last years, genetic, biochemical and structural studies have identified key players involved in both RNA processing pathways and provided the first insights into the underlying mechanisms. Here, we review our current understanding of RNA processing in mammalian mitochondria and provide an outlook on open questions in the field.
人类线粒体拥有一个环状、多倍体基因组（mtDNA），编码 11 种信使 RNA（mRNA）、2 种核糖体 RNA（rRNA）和 22 种转移 RNA（tRNA）。线粒体转录产生长的多顺反子转录本，跨越基因组的几乎整个长度，因此包含所有三种类型的 RNA。初级转录本随后经历了许多加工和成熟步骤，这些步骤构成了线粒体基因表达的关键调控点。线粒体 RNA 加工的第一步包括将初级转录本分离成单个的、功能的 RNA 分子，这可以通过两种不同的途径发生。这两种途径都由专门的分子机制来完成，这些机制与其他地方发现的 RNA 加工酶有很大的不同。因此，其潜在的分子机制仍知之甚少。在过去的几年中，遗传、生化和结构研究已经确定了两种 RNA 加工途径中涉及的关键参与者，并为潜在机制提供了初步的见解。在这里，我们回顾了我们目前对哺乳动物线粒体中 RNA 加工的理解，并对该领域的开放性问题进行了展望。
