title: A truncated hnRNP A1 isoform, lacking the RGG-box RNA binding domain, can efficiently regulate HIV-1 splicing and replication.
abstract: Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is one of the most abundant RNA binding proteins. hnRNP A1 is localized prevalently in the nucleus but it can relocate to the cytoplasm in response to specific stimuli shuttling between nuclear and cytoplasmic compartments. The cellular localization of this protein is regulated by a short C-terminus motif (M9) and other less defined sequences. The RNA binding specificity of this protein is dependent on multiple RNA binding domains (RBDs), which regulate its role in RNA processing and expression. hnRNP A1 plays multiple roles in gene expression by regulating the biogenesis and translation of messengers RNAs, the processing of miRNAs, affecting transcription and controlling telomere maintenance. The multiple functions of this protein correlate with diverse roles in genetic disease, cancer and the replication of viral pathogens. Utilizing a tagged hnRNP A1 deletion library we have shown that the three hnRNP A1 RBDs contribute to the prevalent nuclear distribution of the protein. Our data also indicate that a truncated form of the protein, lacking one of the RBDs, the RGG-box, can regulate splicing of a splicing reporter minigene and down-regulate replication of the HIV-1 virus with efficiency comparable to the wild-type protein. This functional hnRNP A1 deletion mutant is similar to a predicted hnRNP A1 isoform, which had not been previously experimentally characterized.
authors: Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Rd, Boca Raton, FL 33431, USA.
authors: Jacques
authors: J
authors: Jean-Philippe
authors: Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Rd, Boca Raton, FL 33431, USA.
authors: Sean
authors: S
authors: Paz
authors: Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Rd, Boca Raton, FL 33431, USA.
authors: Michael L
authors: ML
authors: Lu
authors: Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Rd, Boca Raton, FL 33431, USA. Electronic address: mcaputi@fau.edu.
authors: Massimo
authors: M
authors: Caputi
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D059372:Nucleotide Motifs / Q000235:genetics; D020033:Protein Isoforms; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics; D017384:Sequence Deletion; D014779:Virus Replication
chemical_list: D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D020033:Protein Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C000619656:hnRNPA1 protein, human
keywords: Alternative splicing; HIV-1; RGG-box; RRM; hnRNP A1