Academic Journal
View in EDS

The SYNGAP1 3'UTR Variant in ALS Patients Causes Aberrant SYNGAP1 Splicing and Dendritic Spine Loss by Recruiting HNRNPK.

Bibliographic Details
Title: The SYNGAP1 3'UTR Variant in ALS Patients Causes Aberrant SYNGAP1 Splicing and Dendritic Spine Loss by Recruiting HNRNPK.
Authors: Satoshi Yokoi, Takuji Ito, Kentaro Sahashi, Masahiro Nakatochi, Ryoichi Nakamura, Genki Tohnai, Yusuke Fujioka, Shinsuke Ishigaki, Tsuyoshi Udagawa, Yuishin Izumi, Mitsuya Morita, Osamu Kano, Masaya Oda, Takefumi Sone, Hideyuki Okano, Naoki Atsuta, Masahisa Katsuno, Yohei Okada, Gen Sobue
Source: Journal of Neuroscience; 11/23/2022, Vol. 42 Issue 47, p8881-8896, 16p
Subject Terms: DENDRITIC spines, MOTOR neurons, AMYOTROPHIC lateral sclerosis, RNA-binding proteins, PLURIPOTENT stem cells
Geographic Terms: JAPAN
Abstract: Fused in sarcoma (FUS) is a pathogenic RNA-binding protein in amyotrophic lateral sclerosis (ALS). We previously reported that FUS stabilizes Synaptic Ras-GTPase activating protein 1 (Syngapl) mRNA at its 3' untranslated region (UTR) and maintains spine maturation. To elucidate the pathologic roles of this mechanism in ALS patients, we identified the SYNGAP1 3'UTR variant rs149438267 in seven (four males and three females) out of 807 ALS patients at the FUS binding site from a multicenter cohort in Japan. Human-induced pluripotent stem cell (hiPSC)-derived motor neurons with the SYNGAP1 variant showed aberrant splicing, increased isoform α1 levels, and decreased isoform y levels, which caused dendritic spine loss. Moreover, the SYNGAP1 variant excessively recruited FUS and heterogeneous nuclear ribonucleoprotein K (HNRNPK), and antisense oligonucleotides (ASOs) blocking HNRNPK altered aberrant splicing and ameliorated dendritic spine loss. These data suggest that excessive recruitment of RNA-binding proteins, especially HNRNPK, as well as changes in SYNGAP1 isoforms, are crucial for spine formation in motor neurons. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Neuroscience is the property of Society for Neuroscience and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Complementary Index
FullText Text:
  Availability: 0
CustomLinks:
  – Url: https://resolver.ebsco.com/c/xy5jbn/result?sid=EBSCO:edb&genre=article&issn=02706474&ISBN=&volume=42&issue=47&date=20221123&spage=8881&pages=8881-8896&title=Journal of Neuroscience&atitle=The%20SYNGAP1%203%27UTR%20Variant%20in%20ALS%20Patients%20Causes%20Aberrant%20SYNGAP1%20Splicing%20and%20Dendritic%20Spine%20Loss%20by%20Recruiting%20HNRNPK.&aulast=Satoshi%20Yokoi&id=DOI:10.1523/JNEUROSCI.0455-22.2022
    Name: Full Text Finder (for New FTF UI) (s8985755)
    Category: fullText
    Text: Find It @ SCU Libraries
    MouseOverText: Find It @ SCU Libraries
Header DbId: edb
DbLabel: Complementary Index
An: 160389255
RelevancyScore: 957
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 957.27880859375
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: The SYNGAP1 3'UTR Variant in ALS Patients Causes Aberrant SYNGAP1 Splicing and Dendritic Spine Loss by Recruiting HNRNPK.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Satoshi+Yokoi%22">Satoshi Yokoi</searchLink><br /><searchLink fieldCode="AR" term="%22Takuji+Ito%22">Takuji Ito</searchLink><br /><searchLink fieldCode="AR" term="%22Kentaro+Sahashi%22">Kentaro Sahashi</searchLink><br /><searchLink fieldCode="AR" term="%22Masahiro+Nakatochi%22">Masahiro Nakatochi</searchLink><br /><searchLink fieldCode="AR" term="%22Ryoichi+Nakamura%22">Ryoichi Nakamura</searchLink><br /><searchLink fieldCode="AR" term="%22Genki+Tohnai%22">Genki Tohnai</searchLink><br /><searchLink fieldCode="AR" term="%22Yusuke+Fujioka%22">Yusuke Fujioka</searchLink><br /><searchLink fieldCode="AR" term="%22Shinsuke+Ishigaki%22">Shinsuke Ishigaki</searchLink><br /><searchLink fieldCode="AR" term="%22Tsuyoshi+Udagawa%22">Tsuyoshi Udagawa</searchLink><br /><searchLink fieldCode="AR" term="%22Yuishin+Izumi%22">Yuishin Izumi</searchLink><br /><searchLink fieldCode="AR" term="%22Mitsuya+Morita%22">Mitsuya Morita</searchLink><br /><searchLink fieldCode="AR" term="%22Osamu+Kano%22">Osamu Kano</searchLink><br /><searchLink fieldCode="AR" term="%22Masaya+Oda%22">Masaya Oda</searchLink><br /><searchLink fieldCode="AR" term="%22Takefumi+Sone%22">Takefumi Sone</searchLink><br /><searchLink fieldCode="AR" term="%22Hideyuki+Okano%22">Hideyuki Okano</searchLink><br /><searchLink fieldCode="AR" term="%22Naoki+Atsuta%22">Naoki Atsuta</searchLink><br /><searchLink fieldCode="AR" term="%22Masahisa+Katsuno%22">Masahisa Katsuno</searchLink><br /><searchLink fieldCode="AR" term="%22Yohei+Okada%22">Yohei Okada</searchLink><br /><searchLink fieldCode="AR" term="%22Gen+Sobue%22">Gen Sobue</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: Journal of Neuroscience; 11/23/2022, Vol. 42 Issue 47, p8881-8896, 16p
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22DENDRITIC+spines%22">DENDRITIC spines</searchLink><br /><searchLink fieldCode="DE" term="%22MOTOR+neurons%22">MOTOR neurons</searchLink><br /><searchLink fieldCode="DE" term="%22AMYOTROPHIC+lateral+sclerosis%22">AMYOTROPHIC lateral sclerosis</searchLink><br /><searchLink fieldCode="DE" term="%22RNA-binding+proteins%22">RNA-binding proteins</searchLink><br /><searchLink fieldCode="DE" term="%22PLURIPOTENT+stem+cells%22">PLURIPOTENT stem cells</searchLink>
– Name: SubjectGeographic
  Label: Geographic Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22JAPAN%22">JAPAN</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Fused in sarcoma (FUS) is a pathogenic RNA-binding protein in amyotrophic lateral sclerosis (ALS). We previously reported that FUS stabilizes Synaptic Ras-GTPase activating protein 1 (Syngapl) mRNA at its 3' untranslated region (UTR) and maintains spine maturation. To elucidate the pathologic roles of this mechanism in ALS patients, we identified the SYNGAP1 3'UTR variant rs149438267 in seven (four males and three females) out of 807 ALS patients at the FUS binding site from a multicenter cohort in Japan. Human-induced pluripotent stem cell (hiPSC)-derived motor neurons with the SYNGAP1 variant showed aberrant splicing, increased isoform α1 levels, and decreased isoform y levels, which caused dendritic spine loss. Moreover, the SYNGAP1 variant excessively recruited FUS and heterogeneous nuclear ribonucleoprotein K (HNRNPK), and antisense oligonucleotides (ASOs) blocking HNRNPK altered aberrant splicing and ameliorated dendritic spine loss. These data suggest that excessive recruitment of RNA-binding proteins, especially HNRNPK, as well as changes in SYNGAP1 isoforms, are crucial for spine formation in motor neurons. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Neuroscience is the property of Society for Neuroscience and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://login.libproxy.scu.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edb&AN=160389255
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1523/JNEUROSCI.0455-22.2022
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 16
        StartPage: 8881
    Subjects:
      – SubjectFull: JAPAN
        Type: general
      – SubjectFull: DENDRITIC spines
        Type: general
      – SubjectFull: MOTOR neurons
        Type: general
      – SubjectFull: AMYOTROPHIC lateral sclerosis
        Type: general
      – SubjectFull: RNA-binding proteins
        Type: general
      – SubjectFull: PLURIPOTENT stem cells
        Type: general
    Titles:
      – TitleFull: The SYNGAP1 3'UTR Variant in ALS Patients Causes Aberrant SYNGAP1 Splicing and Dendritic Spine Loss by Recruiting HNRNPK.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Satoshi Yokoi
      – PersonEntity:
          Name:
            NameFull: Takuji Ito
      – PersonEntity:
          Name:
            NameFull: Kentaro Sahashi
      – PersonEntity:
          Name:
            NameFull: Masahiro Nakatochi
      – PersonEntity:
          Name:
            NameFull: Ryoichi Nakamura
      – PersonEntity:
          Name:
            NameFull: Genki Tohnai
      – PersonEntity:
          Name:
            NameFull: Yusuke Fujioka
      – PersonEntity:
          Name:
            NameFull: Shinsuke Ishigaki
      – PersonEntity:
          Name:
            NameFull: Tsuyoshi Udagawa
      – PersonEntity:
          Name:
            NameFull: Yuishin Izumi
      – PersonEntity:
          Name:
            NameFull: Mitsuya Morita
      – PersonEntity:
          Name:
            NameFull: Osamu Kano
      – PersonEntity:
          Name:
            NameFull: Masaya Oda
      – PersonEntity:
          Name:
            NameFull: Takefumi Sone
      – PersonEntity:
          Name:
            NameFull: Hideyuki Okano
      – PersonEntity:
          Name:
            NameFull: Naoki Atsuta
      – PersonEntity:
          Name:
            NameFull: Masahisa Katsuno
      – PersonEntity:
          Name:
            NameFull: Yohei Okada
      – PersonEntity:
          Name:
            NameFull: Gen Sobue
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 23
              M: 11
              Text: 11/23/2022
              Type: published
              Y: 2022
          Identifiers:
            – Type: issn-print
              Value: 02706474
          Numbering:
            – Type: volume
              Value: 42
            – Type: issue
              Value: 47
          Titles:
            – TitleFull: Journal of Neuroscience
              Type: main
ResultId 1