A novel set of nuclear localization signals determine distributions of the alphaCP RNA-binding proteins.
نویسندگان
چکیده
AlphaCPs comprise a subfamily of KH-domain-containing RNA-binding proteins with specificity for C-rich pyrimidine tracts. These proteins play pivotal roles in a broad spectrum of posttranscriptional events. The five major alphaCP isoforms are encoded by four dispersed loci. Each isoform contains three repeats of the RNA-binding KH domain (KH1, KH2, and KH3) but lacks other identifiable motifs. To explore the complexity of their respective functions, we examined the subcellular localization of each alphaCP isoform. Immunofluorescence studies revealed three distinct distributions: alphaCP1 and alphaCP2 are predominantly nuclear with specific enrichment of alphaCP1 in nuclear speckles, alphaCP3 and alphaCP4 are restricted to the cytoplasm, and alphaCP2-KL, an alphaCP2 splice variant, is present at significant levels in both the nucleus and the cytoplasm. We mapped nuclear localization signals (NLSs) for alphaCP isoforms. alphaCP2 contains two functionally independent NLS. Both NLSs appear to be novel and were mapped to a 9-amino-acid segment between KH2 and KH3 (NLS I) and to a 12-amino-acid segment within KH3 (NLS II). NLS I is conserved in alphaCP1, whereas NLS II is inactivated by two amino acid substitutions. Neither NLS is present in alphaCP3 or alphaCP4. Consistent with mapping studies, deletion of NLS I from alphaCP1 blocks its nuclear accumulation, whereas NLS I and NLS II must both be inactivated to block nuclear accumulation of alphaCP2. These data demonstrate an unexpected complexity in the compartmentalization of alphaCP isoforms and identify two novel NLS that play roles in their respective distributions. This complexity of alphaCP distribution is likely to contribute to the diverse functions mediated by this group of abundant RNA-binding proteins.
منابع مشابه
A Novel Set of Nuclear Localization Signals Determine Distributions of the CP RNA-Binding Proteins
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ورودعنوان ژورنال:
- Molecular and cellular biology
دوره 23 23 شماره
صفحات -
تاریخ انتشار 2003