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pubmed-article:20857263pubmed:abstractTextWe recently reported the chromosome region maintenance 1 (CRM1)-dependent nuclear export of intron-less human interferon-?1 (IFN-?1) mRNA, which encodes a main effecter of host innate immunity. We show that the coding region of IFN-?1 mRNA forms novel secondary structures that are responsible for the CRM1-dependent export of the transcript. Deletion-mutagenesis, in vivo export assays, and computer analyses of the folding potentials of export-competent fragments revealed the presence of a domain, termed the conserved secondary structure (CSS), comprising two adjacent putative stable stem-loop structures (nt 208-452). Internal deletion-mutagenesis and constitutive export assays of each stem-loop structure demonstrated that subregions 308-322 and 352-434 act as a core element by conferring the export function on the CSS. Leptomycin B (LMB) inhibition of the CRM1 pathway decreased the export of core element RNA, implying that the principal site of CRM1 action for exporting IFN-?1 mRNA resides within the core element. An RNPS1 (RNA-binding protein S1, serine-rich domain) cDNA was isolated by yeast three-hybrid screening, using bait containing two CSS regions. We showed that RNPS1 might recognize IFN-?1 mRNP that includes CRM1. The data demonstrate that interaction between RNA structures in the coding region and CRM1 affects the nucleocytoplasmic translocation of IFN-?1 mRNA.lld:pubmed
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pubmed-article:20857263pubmed:articleTitleNovel cis-active structures in the coding region mediate CRM1-dependent nuclear export of IFN-? 1 mRNA.lld:pubmed
pubmed-article:20857263pubmed:affiliationLaboratory of Microbiology and Cell Biology, Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan. kimurato@ph.ritsumei.ac.jplld:pubmed
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