Multiple G-quartet structures in pre-edited mRNAs suggest evolutionary driving force for RNA editing in trypanosomes

• Published in: Scientific reports Vol. 6; no. 1; p. 29810
• Main Authors: Leeder, W.-Matthias, Hummel, Niklas F. C., Göringer, H. Ulrich
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.07.2016; Nature Publishing Group
• Subjects: 45/90; 631/326/417/2550; 631/337/1645/1944; Base Sequence; Cluster analysis; DNA Replication; Editing; Evolution, Molecular; G-Quadruplexes; Gene Expression Regulation; Genomes; Humanities and Social Sciences; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial DNA; Models, Molecular; multidisciplinary; Parasites; Protozoa; RNA Editing; RNA Precursors - chemistry; RNA Precursors - genetics; RNA, Protozoan - chemistry; RNA, Protozoan - genetics; Science; Trypanosoma - classification; Trypanosoma - genetics; Trypanosoma brucei brucei - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep29810

Mitochondrial transcript maturation in African trypanosomes requires a U-nucleotide specific RNA editing reaction. In its most extreme form hundreds of U’s are inserted into and deleted from primary transcripts to generate functional mRNAs. Unfortunately, both origin and biological role of the process have remained enigmatic. Here we report a so far unrecognized structural feature of pre-edited mRNAs. We demonstrate that the cryptic pre-mRNAs contain numerous clustered G-nt, which fold into G-quadruplex (GQ) structures. We identified 27 GQ’s in the different pre-mRNAs and demonstrate a positive correlation between the steady state abundance of guide (g)RNAs and the sequence position of GQ-elements. We postulate that the driving force for selecting G-rich sequences lies in the formation of DNA/RNA hybrid G-quadruplex (HQ) structures between the pre-edited transcripts and the non-template strands of mitochondrial DNA. HQ’s are transcription termination/replication initiation sites and thus guarantee an unperturbed replication of the mt-genome. This is of special importance in the insect-stage of the parasite. In the transcription-on state, the identified GQ’s require editing as a GQ-resolving activity indicating a link between replication, transcription and RNA editing. We propose that the different processes have coevolved and suggest the parasite life-cycle and the single mitochondrion as evolutionary driving forces.