
rbm-26 (RBM26/27) は、MALS-1 (MALSU1) ミトリボソーム組み立て因子の発現を抑制することで、軸索変性から保護する。


coremsg

Mitochondrial dysfunction is thought to be a key component of neurodevelopmental disorders such as autism, intellectual disability, and ADHD. However, little is known about the molecular mechanisms that protect against mitochondrial dysfunction during neurodevelopment. Here, we address this question through the investigation of rbm-26 , the C. elegans ortholog of the RBM27 autism candidate gene, which encodes an RNA-binding protein whose role in neurons is unknown. We report that RBM-26 (RBM26/27) protects against axonal defects by negatively regulating expression of the MALS-1 (MALSU1) mitoribosomal assembly factor. Autism-associated missense variants in RBM-26 cause a sharp decrease in RBM-26 protein expression along with defects in in axon tiling and axon degeneration that occurs during larval development. Using a biochemical screen, we identified the mRNA for the MALS-1 mitoribosomal assembly factor as a binding partner for RBM-26. Loss of RBM-26 function causes a dramatic overexpression of mals-1 mRNA and MALS-1 protein. Moreover, genetic analysis indicates that this overexpression of MALS-1 is responsible for the mitochondrial and axon degeneration defects in rbm-26 mutants. These observations reveal a mechanism that regulates expression of a mitoribosomal assembly factor to protect against axon degeneration during neurodevelopment.

### Competing Interest Statement

The authors have declared no competing interest.

Autism candidate gene rbm-26(RBM26/27) regulates MALS-1 to protect against mitochondrial dysfunction and axon degeneration during neurodevelopment.

自閉症候補遺伝子-rbm-26-rbm26-27-がmalsu-1を調節し-軸索発達時の


自閉症候補遺伝子 rbm-26 (RBM26/27) がMALSU-1を調節し、軸索発達時の
ミトコンドリア機能障害から保護する


自閉症候補遺伝子 rbm-26 (RBM26/27) がMALSU-1を調節し、軸索発達時の ミトコンドリア機能障害から保護する

自閉症候補遺伝子 rbm-26 (RBM26/27) がMALSU-1を調節し、軸索発達時のミトコンドリア機能障害から保護する