期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：44
页码：E10323-E10332
DOI：10.1073/pnas.1808981115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mitochondrial genomes are often transcribed into polycistronic RNAs punctuated by tRNAs whose excision defines mature RNA boundaries. Although kinetoplast DNA lacks tRNA genes, it is commonly held that in Trypanosoma brucei the monophosphorylated 5′ ends of functional molecules typify precursor partitioning by an unknown endonuclease. On the contrary, we demonstrate that individual mRNAs and rRNAs are independently synthesized as 3′-extended precursors. The transcription-defined 5′ terminus is converted into a monophosphorylated state by the pyrophosphohydrolase complex, termed the “PPsome.” Composed of the MERS1 NUDIX enzyme, the MERS2 pentatricopeptide repeat RNA-binding subunit, and MERS3 polypeptide, the PPsome binds to specific sequences near mRNA 5′ termini. Most guide RNAs lack PPsome-recognition sites and remain triphosphorylated. The RNA-editing substrate-binding complex stimulates MERS1 pyrophosphohydrolase activity and enables an interaction between the PPsome and the polyadenylation machinery. We provide evidence that both 5′ pyrophosphate removal and 3′ adenylation are essential for mRNA stabilization. Furthermore, we uncover a mechanism by which antisense RNA-controlled 3′–5′ exonucleolytic trimming defines the mRNA 3′ end before adenylation. We conclude that mitochondrial mRNAs and rRNAs are transcribed and processed as insulated units irrespective of their genomic location.
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