The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs.
How do cells discriminate between selectively edited mRNAs that encode new protein isoforms, and dsRNA-induced, promiscuously edited RNAs that encode nonfunctional, mutant proteins? We have developed a Xenopus oocyte model system which shows that a variety of hyperedited, inosine-containing RNAs are specifically retained in the nucleus. To uncover the mechanism of inosine-induced retention, HeLa cell nuclear extracts were used to isolate a multiprotein complex that binds specifically and cooperatively to inosine-containing RNAs. This complex contains the inosine-specific RNA binding protein p54(nrb), the splicing factor PSF, and the inner nuclear matrix structural protein matrin 3. We provide evidence that one function of the complex identified here is to anchor hyperedited RNAs to the nuclear matrix, while allowing selectively edited mRNAs to be exported.
Zhang
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Department of Microbiology, University of Connecticut Health Center, Farmington, CT 06030, USA.
Carmichael
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D021581:Active Transport, Cell Nucleus / Q000502:physiology; D020816:Amino Acid Motifs; D000818:Animals; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D002846:Chromatography, Affinity; D004268:DNA-Binding Proteins; D015694:Gene Products, rev / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007288:Inosine / Q000737:chemistry / Q000378:metabolism; D008845:Microinjections; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D050810:Octamer Transcription Factors; D009865:Oocytes / Q000502:physiology; D011485:Protein Binding; D017393:RNA Editing / Q000235:genetics / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014466:Ultraviolet Rays; D014982:Xenopus laevis
D004268:DNA-Binding Proteins; D015694:Gene Products, rev; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D050810:Octamer Transcription Factors; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; D007288:Inosine