{"title":"als连锁TDP-43的分子解剖-参与Gly-rich结构域与g -四重体mRNA的相互作用。","authors":"Akira Ishiguro, Nobuyuki Kimura, Takashi Noma, Rieko Shimo-Kon, Akira Ishihama, Takahide Kon","doi":"10.1002/1873-3468.13800","DOIUrl":null,"url":null,"abstract":"<p><p>TDP-43 is the major pathogenic protein of amyotrophic lateral sclerosis (ALS). Previously, we identified that TDP-43 interacts with G-quadruplex (G4)-containing RNA and is involved in their long-distance transport in neurons. For the molecular dissection of the TDP-43 and G4-RNA interaction, we analyzed it here in vitro and in cultured cells using a set of 10 mutant TDP-43 proteins from familial and sporadic ALS patients as well as using the TDP-43 C-terminal Gly-rich domain alone. Our results altogether indicate the involvement of the Gly-rich region of TDP-43 in the initial recognition and binding of G4-RNA, which then induces tight binding of TDP-43 with target RNAs, supposedly in conjunction with its RNA recognition motifs.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"594 14","pages":"2254-2265"},"PeriodicalIF":3.0000,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13800","citationCount":"18","resultStr":"{\"title\":\"Molecular dissection of ALS-linked TDP-43 - involvement of the Gly-rich domain in interaction with G-quadruplex mRNA.\",\"authors\":\"Akira Ishiguro, Nobuyuki Kimura, Takashi Noma, Rieko Shimo-Kon, Akira Ishihama, Takahide Kon\",\"doi\":\"10.1002/1873-3468.13800\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>TDP-43 is the major pathogenic protein of amyotrophic lateral sclerosis (ALS). Previously, we identified that TDP-43 interacts with G-quadruplex (G4)-containing RNA and is involved in their long-distance transport in neurons. For the molecular dissection of the TDP-43 and G4-RNA interaction, we analyzed it here in vitro and in cultured cells using a set of 10 mutant TDP-43 proteins from familial and sporadic ALS patients as well as using the TDP-43 C-terminal Gly-rich domain alone. Our results altogether indicate the involvement of the Gly-rich region of TDP-43 in the initial recognition and binding of G4-RNA, which then induces tight binding of TDP-43 with target RNAs, supposedly in conjunction with its RNA recognition motifs.</p>\",\"PeriodicalId\":50454,\"journal\":{\"name\":\"FEBS Letters\",\"volume\":\"594 14\",\"pages\":\"2254-2265\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2020-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1002/1873-3468.13800\",\"citationCount\":\"18\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"FEBS Letters\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/1873-3468.13800\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2020/5/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/1873-3468.13800","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/5/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Molecular dissection of ALS-linked TDP-43 - involvement of the Gly-rich domain in interaction with G-quadruplex mRNA.
TDP-43 is the major pathogenic protein of amyotrophic lateral sclerosis (ALS). Previously, we identified that TDP-43 interacts with G-quadruplex (G4)-containing RNA and is involved in their long-distance transport in neurons. For the molecular dissection of the TDP-43 and G4-RNA interaction, we analyzed it here in vitro and in cultured cells using a set of 10 mutant TDP-43 proteins from familial and sporadic ALS patients as well as using the TDP-43 C-terminal Gly-rich domain alone. Our results altogether indicate the involvement of the Gly-rich region of TDP-43 in the initial recognition and binding of G4-RNA, which then induces tight binding of TDP-43 with target RNAs, supposedly in conjunction with its RNA recognition motifs.
期刊介绍:
FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.