Author:
Hamad Nesreen,Mashima Tsukasa,Yamaoki Yudai,Kondo Keiko,Yoneda Ryoma,Oyoshi Takanori,Kurokawa Riki,Nagata Takashi,Katahira Masato
Abstract
AbstractTranslocated in liposarcoma (TLS)/fused in sarcoma (FUS) is a multitasking DNA/RNA binding protein implicated in cancer and neurodegenerative diseases. Upon DNA damage, TLS is recruited to the upstream region of the cyclin D1 gene (CCND1) through binding to the promotor associated non-coding RNA (pncRNA) that is transcribed from and tethered at the upstream region. Binding to pncRNA is hypothesized to cause the conformational change of TLS that enables its inhibitive interaction with histone acetyltransferases and resultant repression of CCND1 expression, although no experimental proof has been obtained. Here, the closed-to-open conformational change of TLS on binding pncRNA was implied by fluorescence resonance energy transfer. A small fragment (31 nucleotides) of the full-length pncRNA (602 nucleotides) was shown to be sufficient for the conformational change of TLS. Dissection of pncRNA identified the G-rich RNA sequence that is critical for the conformational change. The length of RNA was also revealed to be critical for the conformational change. Furthermore, it was demonstrated that the conformational change of TLS is caused by another target DNA and RNA, telomeric DNA and telomeric repeat-containing RNA. The conformational change of TLS on binding target RNA/DNA is suggested to be essential for biological functions.
Funder
Ministry of Education, Culture, Sports, Science and Technology,Japan
Ministry of Education, Culture, Sports, Science and Technology
Publisher
Springer Science and Business Media LLC
Reference37 articles.
1. Crozat, A., Åman, P., Mandahl, N. & Ron, D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature 363, 640–644 (1993).
2. Doi, H., Koyano, S., Suzuki, Y., Nukina, N. & Kuroiwa, Y. The RNA-binding protein FUS/TLS is a common aggregate-interacting protein in polyglutamine diseases. Neurosci. Res. 66, 131–133 (2010).
3. Doi, H. et al. Identification of ubiquitin-interacting proteins in purified polyglutamine aggregates. FEBS Lett. 571, 171–176 (2004).
4. Doi, H. et al. RNA-binding protein TLS is a major nuclear aggregate-interacting protein in huntingtin exon 1 with expanded polyglutamine-expressing cells. J. Biol. Chem. 283, 6489–500 (2008).
5. Kwiatkowski, T. J. et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science (80-.). 323, (2009).
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