Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10870085 | FEBS Letters | 2015 | 9 Pages |
Abstract
TDP-43 (TAR DNA binding protein of 43kDa) and its C-terminal fragments are thought to be linked to the pathologies of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Here, we demonstrate that the aggregates or inclusions formed by its 35-kDa fragment (namely TDP-35) sequester full-length TDP-43 into cytoplasmic inclusions; and this sequestration is mediated by binding with RNA that is enriched in the cytoplasmic inclusions. RNA recognition motif 1 (RRM1) of TDP-43/TDP-35 plays a dominant role in nucleic-acid binding; mutation in this moiety abrogates formation of the TDP-35 inclusions and its RNA-assisted association with TDP-43. Thus, TDP-35 is able to sequester TDP-43 from nuclear localization into cytoplasmic inclusions, and RNA binding plays an essential role in this process.
Keywords
TDP-43GFPRNAse ARibonuclease AITCRNPRRMssDNAFTLDdeoxyribonucleaseSingle-strand DNADNAseRNA recognition motifamyotrophic lateral sclerosisRNA immunoprecipitationImmunofluorescenceALSfrontotemporal lobar degenerationribonucleoproteinfluorescent in situ hybridizationFishRIPgreen fluorescent proteinIsothermal titration calorimetry
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Authors
Mei-Xia Che, Lei-Lei Jiang, Hai-Yin Li, Ya-Jun Jiang, Hong-Yu Hu,