RNA-DNA differences in human mitochondria restore ancestral form of 16S ribosomal RNA

Dan Bar-Yaacov, Gal Avital, Liron Levin, Allison L. Richards, Naomi Hachen, Boris Rebolledo Jaramillo, Anton Nekrutenko, Raz Zarivach, Dan Mishmar

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים


RNA transcripts are generally identical to the underlying DNA sequences. Nevertheless, RNA-DNA differences (RDDs) were found in the nuclear human genome and in plants and animals but not in human mitochondria. Here, by deep sequencing of human mitochondrial DNA (mtDNA) and RNA, we identified three RDD sites at mtDNA positions 295 (C-to-U), 13710 (A-to-U, A-to-G), and 2617 (A-to-U, A-to-G). Position 2617, within the 16S rRNA, harbored the most prevalent RDDs (>30% A-to-U and ~15% A-to-G of the reads in all tested samples). The 2617 RDDs appeared already at the precursor polycistrone mitochondrial transcript. By using traditional Sanger sequencing, we identified the A-to-U RDD in six different cell lines and representative primates (Gorilla gorilla, Pongo pigmaeus, and Macaca mulatta), suggesting conservation of the mechanism generating such RDD. Phylogenetic analysis of more than 1700 vertebrate mtDNA sequences supported a thymine as the primate ancestral allele at position 2617, suggesting that the 2617 RDD recapitulates the ancestral 16S rRNA. Modeling U or G (the RDDs) at position 2617 stabilized the large ribosomal subunit structure in contrast to destabilization by an A (the pre-RDDs). Hence, these mitochondrial RDDs are likely functional.

שפה מקוריתאנגלית אמריקאית
עמודים (מ-עד)1789-1796
מספר עמודים8
כתב עתGenome Research
מספר גיליון11
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 1 נוב׳ 2013

ASJC Scopus subject areas

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