Precise Annotation And Functional Study Of Control Regions In Mammalian Mitochondrial Genomes

As the main place of aerobic respiration,mitochondria can provide energy for life activities.Animal mitochondrial genomes generally contain at least one control region,which is thought to be involved in the regulation of mitochondrial transcription and replication,but the exact regulatory mechanism remains to be studied.In this study,the mitochondrial genomes of 4 mammalian species(human,chimpanzee,rhesus monkey,and mouse)were annotated using the "precise annotation",and the functions of mammalian mitochondrial genome control regions were preliminarily discussed..1.According to the precise annotation of 4 mammalian mitochondrial genomes,especially the precise annotation of the transcription initiation site and the transcription termination site,the uninterruptable transcription model of mitochondrial genome has been verified in mammals and proved to be widespread in mammals.2.Based on precise annotation,siRNA interference technology was used to preliminarily verify the biological function of transcripts in mammalian mitochondrial genome control region,and it was found that 5' end small RNA of lnc RNA MDL1 and MDL1 AS could lead to the decrease of mitochondrial gene expression and reduce cell survival rate.The results preliminarily indicate that the transcriptions of mammalian mitochondrial genome control region may be involved in the regulation of mitochondrial genome transcription by negative feedback mechanism.3.Based on amplon sequencing and bioinformatics analysis,we found that the number and variety of mutations in the CSB2 region of the mitochondrial genome of tumor cells are much greater than currently recognized.Therefore,we tried to explain the Warburg effect from the perspective of mutations in(but not limited)the CSB2 region of the mitochondrial genome.4.A method based on qPCR to detect the expression changes of two sets of genes(apoptose-related genes and mitochondrial genes)was established to preliminarily detect the cell apoptosis through mitochondria passway,then this method was used to try to explore whether the G-quadruplet targeted drugs could act on the CSB2 region of the mitochondrial genome of tumor cells and cause cell apoptosis.In conclusion,precise annotation of mitochondrial genome is beneficial to the study of mitochondrial gene function and the discovery of new genes.This study is of great significance for the study on the function of mammalian mitochondrial control region and the regulation mechanism of mitochondrial replication and transcription.