Non-coding transcript in T cells (NTT): antisense transcript activates PKR and NF-kappaB in human lymphocytes.
T cell activation is a complex process involving many steps and the role played by the non-protein-coding RNAs (ncRNAs) in this phenomenon is still unclear. The non-coding T cells transcript (NTT) is differentially expressed during human T cells activation, but its function is unknown. Here, we detected a 426 nt NTT transcript by RT-PCR using RNA of human lymphocytes activated with a synthetic peptide of HIV-1. After cloning, the sense and antisense 426 nt NTT transcripts were obtained by in vitro transcription and were sequenced. We found that both transcripts are highly structured and are able to activate PKR. A striking observation was that the antisense 426 nt NTT transcript is significantly more effective in activating PKR than the corresponding sense transcript. The transcription factor NF-kappaB is activated by PKR through phosphorylation and subsequent degradation of its inhibitor I-kappaBbeta. We also found that the antisense 426 nt NTT transcript induces more efficiently the degradation of I-kappaBbeta than the sense transcript. Thus, this study suggests that the role played by NTT in the activation of lymphocytes can be mediated by PKR through NF-kappaB activation. However, the physiological significance of the activity of the antisense 426 nt NTT transcript remains unknown.
Delgado André
Nayara
N
Department of Biochemistry and Immunology, School of Medicine University of São Paulo, 14049-900 Ribeirão Preto, SP., Brazil.
De Lucca
Fernando L
FL
D004789:Enzyme Activation; D015497:HIV-1 / Q000276:immunology; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic; D019892:eIF-2 Kinase / Q000378:metabolism*
D054298:Human Immunodeficiency Virus Proteins; D016328:NF-kappa B; D010455:Peptides; D016372:RNA, Antisense; D022661:RNA, Untranslated; D019892:eIF-2 Kinase