RNA-binding protein TLS is a major nuclear aggregate-interacting protein in Huntingtin exon 1 with expanded polyglutamine-expressing cells

Hiroshi Doi, Kazumasa Okamura, Peter O. Bauer, Yoshiaki Furukawa, Hideaki Shimizu, Masaru Kurosawa, Yoko Machida, Haruko Miyazaki, Kenichi Mitsui, Yoshiyuki Kuroiwa, Nobuyuki Nukina

Research output: Contribution to journalArticle

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Abstract

Formation of intracellular aggregates is the hallmark of polyglutamine (polyQ) diseases. We analyzed the components of purified nuclear polyQ aggregates by mass spectrometry. As a result, we found that the RNA-binding protein translocated in liposarcoma (TLS) was one of the major components of nuclear polyQ aggregate-interacting proteins in a Huntington disease cell model and was also associated with neuronal intranuclear inclusions of R6/2 mice. In vitro study revealed that TLS could directly bind to truncated N-terminal huntingtin (tNhtt) aggregates but could not bind to monomer GST-tNhtt with 18, 42, or 62Q, indicating that the tNhtt protein acquired the ability to sequester TLS after forming aggregates. Thioflavin T assay and electron microscopic study further supported the idea that TLS bound to tNhtt-42Q aggregates at the early stage of tNhtt-42Q amyloid formation. Immunohistochemistry showed that TLS was associated with neuronal intranuclear inclusions of Huntington disease human brain. Because TLS has a variety of functional roles, the sequestration of TLS to polyQ aggregates may play a role in diverse pathological changes in the brains of patients with polyQ diseases.

Original languageEnglish
Pages (from-to)6489-6500
Number of pages12
JournalJournal of Biological Chemistry
Volume283
Issue number10
DOIs
Publication statusPublished - 2008 Mar 7
Externally publishedYes

Fingerprint

Liposarcoma
RNA-Binding Proteins
Exons
Proteins
Huntington Disease
Brain
Intranuclear Inclusion Bodies
Aptitude
polyglutamine
Huntingtin Protein
Protein Aggregates
Amyloid
Mass spectrometry
Assays
Mass Spectrometry
Monomers
Immunohistochemistry
Electrons

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

RNA-binding protein TLS is a major nuclear aggregate-interacting protein in Huntingtin exon 1 with expanded polyglutamine-expressing cells. / Doi, Hiroshi; Okamura, Kazumasa; Bauer, Peter O.; Furukawa, Yoshiaki; Shimizu, Hideaki; Kurosawa, Masaru; Machida, Yoko; Miyazaki, Haruko; Mitsui, Kenichi; Kuroiwa, Yoshiyuki; Nukina, Nobuyuki.

In: Journal of Biological Chemistry, Vol. 283, No. 10, 07.03.2008, p. 6489-6500.

Research output: Contribution to journalArticle

Doi, H, Okamura, K, Bauer, PO, Furukawa, Y, Shimizu, H, Kurosawa, M, Machida, Y, Miyazaki, H, Mitsui, K, Kuroiwa, Y & Nukina, N 2008, 'RNA-binding protein TLS is a major nuclear aggregate-interacting protein in Huntingtin exon 1 with expanded polyglutamine-expressing cells', Journal of Biological Chemistry, vol. 283, no. 10, pp. 6489-6500. https://doi.org/10.1074/jbc.M705306200
Doi, Hiroshi ; Okamura, Kazumasa ; Bauer, Peter O. ; Furukawa, Yoshiaki ; Shimizu, Hideaki ; Kurosawa, Masaru ; Machida, Yoko ; Miyazaki, Haruko ; Mitsui, Kenichi ; Kuroiwa, Yoshiyuki ; Nukina, Nobuyuki. / RNA-binding protein TLS is a major nuclear aggregate-interacting protein in Huntingtin exon 1 with expanded polyglutamine-expressing cells. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 10. pp. 6489-6500.
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