RNA nucleotide repeats induce mitochondrial dysfunction and the ribosome associated quality control
Teixeira, J.; Harju, A.-M.; Othman, A.; Eriksson, O.; Brandao, A. S.; Battersby, B.; Garcia, S. M. D. A.
Show abstract
Nucleotide repeat sequences are prevalent in the genome and expansion of these sequences is associated with more than 40 neuromuscular disorders. To understand the pathogenic mechanisms underlying RNA-repeat toxicity, we performed a genetic screen in a Caenorhabditis elegans model expressing an expanded CUG repeat specifically in the muscle. Here, we show that expression of this RNA repeat impairs motility by mitochondrial dysfunction, disrupting mitochondrial morphology and respiration. The phenotype is dependent on the RNA-binding factor MBL-1 and requires factors from the ribosome-associated protein quality control complex. Furthermore, Coenzyme Q supplementation rescued the motility impairment and all of the mitochondrial phenotypes. Together, our data reveal the importance of mitochondrial dysfunction in the molecular pathogenesis of RNA repeat expansion disorders.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans 97%
- A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage 96%
- Ether Lipid Biosynthesis Promotes Lifespan Extension and Enables Diverse Prolongevity Paradigms 96%
Similar papers in this journal
- Nuclear receptor NHR-49 promotes peroxisome proliferation to compensate for aldehyde dehydrogenase deficiency in C. elegans 96%
- DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence 95%
- Inactivation of the mitochondrial protease Afg3l2 results in severely diminished respiratory chain activity and widespread defects in mitochondrial gene expression 95%
Similar papers in this journal
- Nutritional vitamin B12 regulates RAS/MAPK-mediated cell fate decisions through the one-carbon metabolism 97%
- A C. elegans model of C9orf72-associated ALS/FTD uncovers a conserved role for eIF2D in RAN translation 96%
- A secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.