TDP-35 sequesters TDP-43 into cytoplasmic inclusions through binding with RNA

Mei Xia Che, Lei Lei Jiang, Hai Yin Li, Ya Jun Jiang, Hong Yu Hu

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number37221
Pages (from-to)1920-1928
Number of pages9
JournalFEBS Letters
Volume589
Issue number15
DOIs
StatePublished - Jul 3 2015

Bibliographical note

Funding Information:
This work was supported by National Basic Research Program of China (Grants 2012CB911003 and 2011CB911104 ) and National Natural Science Foundation of China (Grant 31270773 ).

Keywords

  • C-terminal fragment of ∼35kDa
  • Cytoplasmic inclusion
  • RNA recognition motif
  • Sequestration
  • TAR DNA binding protein of 43kDa

Fingerprint Dive into the research topics of 'TDP-35 sequesters TDP-43 into cytoplasmic inclusions through binding with RNA'. Together they form a unique fingerprint.

Cite this