ArticleProceedings of the National Academy of Sciences of the United States of America2012
Correcting human mitochondrial mutations with targeted RNA import.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Noncoding RNA as potential therapeutics to rescue mitochondrial dysfunction in cardiovascular diseases.American journal of physiology. Heart and circulatory physiology · 2025Pooled it
- Targeting mtDNA to Modulate Mitochondrial Dysfunction in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Gene Therapy Tools for Diseases Caused by Mutations of the Mitochondrial Genome.International journal of molecular sciences · 2026Review
- Towards CRISPR-based editing of the mitochondrial genome in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Skeletal Muscle Mitochondria Contain Nuclear-Encoded RNA Species Prior to and Following Adaptation to Exercise Training in Rats.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Engineered mitochondria in diseases: mechanisms, strategies, and applications.Signal transduction and targeted therapy · 2025Review
- The mitochondrial long non-coding RNA lncMtloop regulates mitochondrial transcription and suppresses Alzheimer's disease.The EMBO journal · 2024Article
- Trafficking of mitochondrial double-stranded RNA from mitochondria to the cytosol.Life science alliance · 2024Article
- Mitochondrial sequencing identifies long noncoding RNA features that promote binding to PNPase.American journal of physiology. Cell physiology · 2024Article
- Mitochondrial diseases and mtDNA editing.Genes & diseases · 2024Review
- Mitochondrial transport of catalytic RNAs and targeting of the organellar transcriptome in human cells.Journal of molecular cell biology · 2024Article
- The Roles of CircRNAs in Mitochondria.Journal of Cancer · 2024Review
- Research progress in mitochondrial gene editing technology.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
- Overcoming the Limitations of CRISPR-Cas9 Systems inMicroorganisms · 2023Review
- A Correlation between 3'-UTR ofJournal of fungi (Basel, Switzerland) · 2023Article
- Mitochondrion-targeted RNA therapies as a potential treatment strategy for mitochondrial diseases.Molecular therapy. Nucleic acids · 2022Review
- Site-specific CRISPR-based mitochondrial DNA manipulation is limited by gRNA import.Scientific reports · 2022Article
- Mitochondrial genome engineering coming-of-age.Trends in genetics : TIG · 2022Review
- Activity and Function in Human Cells of the Evolutionary Conserved Exonuclease Polynucleotide Phosphorylase.International journal of molecular sciences · 2022Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects, and aging. An efficient and simple mechanism for neutralizing deleterious mitochondrial DNA (mtDNA) alterations has unfortunately remained elusive. Here, we report that a 20-ribonucleotide stem-loop sequence from the H1 RNA, the RNA component of the human RNase P enzyme, appended to a nonimported RNA directs the import of the resultant RNA fusion transcript into human mitochondria. The methodology is effective for both noncoding RNAs, such as tRNAs, and mRNAs. The RNA import component, polynucleotide phosphorylase (PNPASE), facilitates transfer of this hybrid RNA into the mitochondrial matrix. In addition, nucleus-encoded mRNAs for mitochondrial proteins, such as the mRNA of human mitochondrial ribosomal protein S12 (MRPS12), contain regulatory sequences in their 3'-untranslated region (UTR) that confers localization to the mitochondrial outer membrane, which is postulated to aid in protein translocation after translation. We show that for some mitochondrial-encoded transcripts, such as COX2, a 3'-UTR localization sequence is not required for mRNA import, whereas for corrective mitochondrial-encoded tRNAs, appending the 3'-UTR localization sequence was essential for efficient fusion-transcript translocation into mitochondria. In vivo, functional defects in mitochondrial RNA (mtRNA) translation and cell respiration were reversed in two human disease lines. Thus, this study indicates that a wide range of RNAs can be targeted to mitochondria by appending a targeting sequence that interacts with PNPASE, with or without a mitochondrial localization sequence, providing an exciting, general approach for overcoming mitochondrial genetic disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.