A new tool for quantifying mitochondrial RNA processing intermediates reveals increased levels of immature mRNA species under oxidative stress

Immature mitochondrial mRNAs with uncleaved 5' tRNA extensions are selectively elevated in mouse hearts lacking mitochondrial superoxide dismutase 2 (SOD2), linking an imRNA signature to oxidative stress.

• Why it matters: Multigene mitochondrial transcripts generate maturation intermediates, but their abundance and relationship to mitochondrial stress are poorly defined, limiting interpretation of RNA-seq results.
• What they did: The team used direct RNA sequencing of intact RNA from healthy mouse hearts to define imRNAs, then built a computational tool to estimate them from short-read RNA-seq; they tested SOD2-deficient hearts and multiple other mouse models, plus rotenone-treated human induced pluripotent stem cells.
• The result: SOD2 deficiency increased imRNAs retaining 5' tRNA extensions without raising 3' extension–retaining species, a pattern not seen in most respiration/transcription/translation/proteostasis models but reproduced by rotenone in human cells.

AI summary of the abstract · may contain errors · not medical advice · read the paper.