title: AU-A, an RNA-binding activity distinct from hnRNP A1, is selective for AUUUA repeats and shuttles between the nucleus and the cytoplasm.
abstract: The 3'-untranslated regions of many labile transcripts contain AU-rich sequences that serve as cis determinants of mRNA stability and translational efficiency. Using a photocrosslinking technique, our laboratory has previously defined three cytoplasmic RNA-binding activities specific for the AUUUA multimers found in the 3'-untranslated regions of lymphokine mRNAs. One of these activities, AU-A, has an apparent molecular mass of 34 kDa, is constitutively expressed in both primary T cells and the Jurkat T cell leukemia line, and binds to a variety of U-rich RNA sequences. Previous studies had shown that AU-A is more prevalent in the nucleus than the cytoplasm, raising the possibility that AU-A is really a nuclear RNA-binding activity that is found in cytoplasmic extracts because of nuclear leakage during cell fractionation. We now show that AU-A shuttles between the cytoplasm and the nucleus. Our results indicate that AU-A is a candidate protein component of ribonucleoprotein complexes that participate in nucleocytoplasmic transport of mRNA and cytoplasmic mRNA metabolism. The properties of AU-A activity are similar to those of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). However, using monoclonal antibodies to hnRNP A1 and protease digestion patterns, we show that AU-A activity and hnRNP A1 protein are distinct. These studies have also allowed us to define a fourth RNA-binding activity of apparent molecular mass 41 kDa with specificity for AUUUA multimers. This activity is restricted to the nucleus and contains the hnRNP C protein.
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637.
authors.forename: D A
authors.initials: DA
authors.lastname: Katz
authors.forename: N G
authors.initials: NG
authors.lastname: Theodorakis
authors.forename: D W
authors.initials: DW
authors.lastname: Cleveland
authors.forename: T
authors.initials: T
authors.lastname: Lindsten
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
mesh_terms: D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D012261:Ribonucleoproteins / Q000378:metabolism*
chemical_list: D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins