AU RNA-binding factors differ in their binding specificities and affinities.
AUUUA multimers present in the 3'-untranslated region of mature lymphokine and cytokine transcripts have been implicated in the regulation of mRNA stability and translational efficiency. We have identified RNA-binding factors, termed AU-A, AU-B, and AU-C, that interact with AUUUA multimers. AU-A is an abundant, constitutively expressed 34-kDa factor that localizes primarily to the nucleus. AU-A binds to AUUUA multimers with low relative affinity and also binds to other U-rich sequences, including a poly(U) sequence. AU-B and AU-C are 30- and 43-kDa cytoplasmic factors that are induced following T cell receptor-mediated stimulation of purified human T cells and bind to AUUUA multimers with high affinity. Protease cleavage of AU-A, AU-B, and AU-C RNA-protein complexes indicate that AU-B and AU-C are structurally related to each other but distinct from AU-A. AU-B and AU-C require three or more tandem AUUUA repeats for efficient binding, and binding by these factors poorly tolerates mutations in the AUUUA recognition sequence. The precise binding specificity, high affinity, pattern of induction, and cytoplasmic localization all suggest that the structurally related AU-B and AU-C RNA-binding factors could be cytoplasmic regulators of lymphokine mRNA metabolism.
Bohjanen
P R
PR
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor 48109.
Petryniak
B
B
June
C H
CH
Thompson
C B
CB
Lindsten
T
T
D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001483:Base Sequence; D017252:CD3 Complex; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D016601:RNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012091:Repetitive Sequences, Nucleic Acid; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D014158:Transcription, Genetic
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D009838:Oligodeoxyribonucleotides; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell