Qki5 safeguards spinal motor neuron function by defining the motor neuron-specific transcriptome via pre-mRNA processing.
Yoshika Hayakawa-YanoTakako FurukawaTsuyoshi MatsuoTakahisa OgasawaraMasahiro NogamiKazumasa YokoyamaMasato YugamiMunehisa ShinozakiChihiro NakamotoKenji SakimuraAkihide KoyamaKazuhiro OgiOsamu OnoderaHirohide TakebayashiHideyuki OkanoMasato YanoPublished in: Proceedings of the National Academy of Sciences of the United States of America (2024)
Many RNA-binding proteins (RBPs) are linked to the dysregulation of RNA metabolism in motor neuron diseases (MNDs). However, the molecular mechanisms underlying MN vulnerability have yet to be elucidated. Here, we found that such an RBP, Quaking5 (Qki5), contributes to formation of the MN-specific transcriptome profile, termed "MN-ness," through the posttranscriptional network and maintenance of the mature MNs. Immunohistochemical analysis and single-cell RNA sequencing (scRNA-seq) revealed that Qki5 is predominantly expressed in MNs, but not in other neuronal populations of the spinal cord. Furthermore, comprehensive RNA sequencing (RNA-seq) analyses revealed that Qki5-dependent RNA regulation plays a pivotal role in generating the MN-specific transcriptome through pre-messenger ribonucleic acid (mRNA) splicing for the synapse-related molecules and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signaling pathways. Indeed, MN-specific ablation of the Qki5 caused neurodegeneration in postnatal mice and loss of Qki5 function resulted in the aberrant activation of stress-responsive JNK/SAPK pathway both in vitro and in vivo. These data suggested that Qki5 plays a crucial biological role in RNA regulation and safeguarding of MNs and might be associated with pathogenesis of MNDs.
Keyphrases
- single cell
- rna seq
- spinal cord
- high throughput
- signaling pathway
- room temperature
- protein kinase
- transition metal
- metal organic framework
- induced apoptosis
- cell death
- climate change
- gene expression
- neuropathic pain
- spinal cord injury
- adipose tissue
- dna methylation
- big data
- insulin resistance
- tyrosine kinase
- cell proliferation
- deep learning
- data analysis
- ionic liquid