Alternative titles; symbols
Cytogenetic location: 6q23-q24 Genomic coordinates (GRCh38): 6:130,000,001-148,500,000
NTT is a member of a family of genes that are transcribed but not translated. Other examples include the genes XIST (314670), IPW (601491), and H19 (103280). Unlike other noncoding transcripts, NTT is transcribed from both alleles (Liu et al., 1997).
Using differential display RT-PCR to screen for mRNAs induced by stimulation of T cells, Liu et al. (1997) identified a novel gene, which they named NTT for 'noncoding transcript in T cells.' Sequencing of the NTT cDNA and genomic DNA revealed that the gene has no exons and is transcribed as a polyadenylated 17-kb mRNA. The sequence contains no significant open reading frames, and computer analysis predicted no coding regions; most of the sequence consists of repetitive elements. RT-PCR showed no cell lines other than T cells expressing NTT. RT-PCR of fractionated T cells showed that the NTT transcript is present predominantly in the nucleus. Southern blot analysis revealed that NTT is a single-copy gene in the human genome and demonstrated single-copy cross-hybridizing bands in monkey and dog.
Liu et al. (1997) determined that the NTT gene has no exons.
By fluorescence in situ hybridization, Liu et al. (1997) mapped the NTT gene to human chromosome 6q23-q24, close to the interferon-gamma receptor gene (107470). Because of their proximity and shared expression pattern, Liu et al. (1997) suggested that these genes may have a functional relationship.
Using RT-PCR analysis, Amarante et al. (2005) showed that a synthetic peptide of human immunodeficiency virus (HIV; see 609423) activated human HLA-A2 blood mononuclear cells and induced expression of NTT.
Using RT-PCR analysis, Yang et al. (2018) showed that NTT was expressed in resting human primary monocytes, monocyte-derived macrophages, and THP-1 cells. The authors identified potential binding motifs for C/EBP-beta (CEBPB; 189965) in the promoter of NTT, and chromatin immunoprecipitation analysis confirmed that C/EBP-beta bound to 3 positions in the NTT promoter and regulated NTT expression in THP-1 cells. NTT acted in cis on genes in its proximity and regulated their expression. In particular, NTT enhanced expression of the downstream gene PBOV1 (605669) by interacting with HNRNPU (602869), which also bound to 2 positions in the PBOV1 promoter region. RT-PCR analysis revealed that C/EBP-beta, NTT, and PBOV1 expression was highly elevated in peripheral blood mononuclear cells of untreated rheumatoid arthritis (RA; 180300) patients, and the higher expression levels appeared to be associated with higher disease inflammatory status. Overexpression of PBOV1 in THP-1 cells resulted in cell-cycle arrest at G1 phase and promoted differentiation towards macrophages and increased CXCL10 (147310) secretion.
Amarante, M. K., De Lucca, F. L., Coral del Oliveira, C. E., Pelegrinelli Fungaro, M. H., Vissoci Reiche, E. M., Muxel, S. M., Ehara Watanabe, M. A. Expression of noncoding mRNA in human blood cells activated with synthetic peptide of HIV. Blood Cells Mol. Dis. 35: 286-290, 2005. [PubMed: 16027015] [Full Text: https://doi.org/10.1016/j.bcmd.2005.06.004]
Liu, A. Y., Torchia, B. S., Migeon, B. R., Siliciano, R. F. The human NTT gene: identification of a novel 17-kb noncoding nuclear RNA expressed in activated CD4+ T cells. Genomics 39: 171-184, 1997. [PubMed: 9027504] [Full Text: https://doi.org/10.1006/geno.1996.4463]
Yang, C.-A., Li, J.-P., Yen, J.-C., Lai, I-L., Ho, Y.-C., Lan, J.-L., Chang, J.-G. lncRNA NTT/PBOV1 axis promotes monocyte differentiation and is elevated in rheumatoid arthritis. Int. J. Molec. Sci. 19: 2806, 2018. [PubMed: 30231487] [Full Text: https://doi.org/10.3390/ijms19092806]