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Qki5 safeguards spinal motor neuron function by defining the motor neuron-specific transcriptome via pre-mRNA processing.
Hayakawa-Yano, Yoshika; Furukawa, Takako; Matsuo, Tsuyoshi; Ogasawara, Takahisa; Nogami, Masahiro; Yokoyama, Kazumasa; Yugami, Masato; Shinozaki, Munehisa; Nakamoto, Chihiro; Sakimura, Kenji; Koyama, Akihide; Ogi, Kazuhiro; Onodera, Osamu; Takebayashi, Hirohide; Okano, Hideyuki; Yano, Masato.
Afiliación
  • Hayakawa-Yano Y; Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Chuo-ku, Niigata 951-8510, Japan.
  • Furukawa T; Keio University Regenerative Medicine Research Center, Kawasaki, Kanagawa 210-0821, Japan.
  • Matsuo T; Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
  • Ogasawara T; Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Chuo-ku, Niigata 951-8510, Japan.
  • Nogami M; The Shonan Incubation Laboratory, Shonan Research Center, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251-8555, Japan.
  • Yokoyama K; The Shonan Incubation Laboratory, Shonan Research Center, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251-8555, Japan.
  • Yugami M; The Shonan Incubation Laboratory, Shonan Research Center, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251-8555, Japan.
  • Shinozaki M; The Shonan Incubation Laboratory, Shonan Research Center, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251-8555, Japan.
  • Nakamoto C; The Shonan Incubation Laboratory, Shonan Research Center, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251-8555, Japan.
  • Sakimura K; Keio University Regenerative Medicine Research Center, Kawasaki, Kanagawa 210-0821, Japan.
  • Koyama A; Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
  • Ogi K; Department of Animal Model Development, Brain Research Institute, Niigata University, Chuo-ku, Niigata 951-8585, Japan.
  • Onodera O; Department of Animal Model Development, Brain Research Institute, Niigata University, Chuo-ku, Niigata 951-8585, Japan.
  • Takebayashi H; Division of Legal Medicine, Department of Community Preventive Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Chuo-ku, Niigata 951-8510, Japan.
  • Okano H; The Shonan Incubation Laboratory, Shonan Research Center, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251-8555, Japan.
  • Yano M; Department of Neurology, Brain Research Institute, Niigata University, Chuo-ku, Niigata 951-8585, Japan.
Proc Natl Acad Sci U S A ; 121(37): e2401531121, 2024 Sep 10.
Article en En | MEDLINE | ID: mdl-39226364
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Médula Espinal / Proteínas de Unión al ARN / Transcriptoma / Neuronas Motoras Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Médula Espinal / Proteínas de Unión al ARN / Transcriptoma / Neuronas Motoras Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos