Premium
TDP‐35 sequesters TDP‐43 into cytoplasmic inclusions through binding with RNA
Author(s) -
Che Mei-Xia,
Jiang Lei-Lei,
Li Hai-Yin,
Jiang Ya-Jun,
Hu Hong-Yu
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.06.009
Subject(s) - rna , frontotemporal lobar degeneration , cytoplasm , cytoplasmic inclusion , nucleic acid , chemistry , microbiology and biotechnology , rna binding protein , biology , biophysics , biochemistry , frontotemporal dementia , gene , pathology , medicine , dementia , disease
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.