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S1-1/RBM10: Multiplicity and Cooperativity of Nuclear Localization Domains.
MedLine Citation:
PMID:  23294349     Owner:  NLM     Status:  Publisher    
BACKGROUND INFORMATION: S1-1, also called RBM10, is an RNA-binding protein of 852 residues. An alteration of its activity causes TARP syndrome, a severe X-linked disorder with pre- or post-natal lethality in affected males. Its molecular function, although still largely unknown, has been suggested to be transcription and alternative splicing. In fact, S1-1 localizes in the nucleus in tissue cells and cultured cells. RESULTS: By deletion and substitution mutagenesis, a classical 17-amino acid nuclear localization sequence (NLS1) was identified at amino acid (aa) 743-759 in the C-terminal region of S1-1. NLS1 was bipartite, with its N-terminal basic cluster weakly contributing to the NLS activity. S1-1 contained two additional NLSs. One was in the aa 60-136 RNA recognition motif region (NLS2), and the other was a novel NLS motif sequence in the aa 481-540 octamer repeat region (NLS3). The octamer repeat is a domain known to be critical in splicing regulation, as shown with RBM5, a close homologue of RBM10 (Bonnal et al., Mol. Cell 32, 81-95, 2008). The NLS activities were verified by expressing each DNA sequence linked to EGFP or a FLAG tag. These multiple NLSs acted cooperatively, and S1-1 became completely cytoplasmic after the concomitant removal of all NLS domains. In some cell types, however, S1-1 was partly cytoplasmic, suggesting that cellular localization of S1-1 is subjected to regulation. CONCLUSIONS: The present results indicate that S1-1 contains multiple NLSs that act cooperatively. Among them, the octamer repeat is a hitherto unreported NLS. The nuclear localization of S1-1 appears to be regulated under certain circumstances. We discuss these NLSs in relation to the biochemical processes they are involved in.
Sheng-Jun Xiao; Ling-Yu Wang; Masatsugu Kimura; Hirotada Kojima; Hiroyuki Kunimoto; Fumiko Nishiumi; Naoki Yamamoto; Koji Nishio; Shunsuke Fujimoto; Takayuki Kato; Seiichi Kitagawa; Hideo Yamane; Koichi Nakajima; Akira Inoue
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-8
Journal Detail:
Title:  Biology of the cell / under the auspices of the European Cell Biology Organization     Volume:  -     ISSN:  1768-322X     ISO Abbreviation:  Biol. Cell     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8108529     Medline TA:  Biol Cell     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Soçiété Francaise des Microscopies and Société de Biologie Cellulaire de France.
Departments of Immunology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; Departments of Pathology, Guilin Medical University, Guilin, P. R. China 541004.
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