Molecular dissection of ALS‐linked TDP‐43 – involvement of the Gly‐rich domain in interaction with G‐quadruplex mRNA
| Autor: | Takahide Kon, Akira Ishihama, Rieko Shimo-Kon, Nobuyuki Kimura, Akira Ishiguro, Takashi Noma |
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| Rok vydání: | 2020 |
| Předmět: |
Mutant
Glycine Biophysics Dissection (medical) G-quadruplex Biochemistry RNA Transport 03 medical and health sciences Protein Domains Structural Biology mental disorders Genetics medicine Humans MRNA transport RNA Messenger Amyotrophic lateral sclerosis Molecular Biology 030304 developmental biology 0303 health sciences Messenger RNA Chemistry Amyotrophic Lateral Sclerosis 030302 biochemistry & molecular biology nutritional and metabolic diseases RNA Cell Biology medicine.disease In vitro nervous system diseases Cell biology DNA-Binding Proteins G-Quadruplexes HEK293 Cells Mutation |
| Zdroj: | FEBS Letters. 594:2254-2265 |
| ISSN: | 1873-3468 0014-5793 |
| DOI: | 10.1002/1873-3468.13800 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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