THE HUMAN NTT GENE - IDENTIFICATION OF A NOVEL 17-KB NONCODING NUCLEAR-RNA EXPRESSED IN ACTIVATED CD4(-CELLS() T)

We describe the cloning and characterization of the NTT gene (noncodin g transcript in T cells), identified by differential display RT-PCR ba sed on the differential presence of its transcript in a subset of acti vated, human CD4(+) T-cell clones. The full-length cDNA and genomic se quences were cloned and found to produce a 17-kb transcript that is po lyadenylated, but is not spliced. Consistent with the transcript's nuc lear predominance, NTT has no open reading frame larger than 270 bp. I t is transcribed in a select subset of CD4(+) T-cell clones propagated in vitro. Its transcription can also be induced in freshly isolated T cells by in vitro activation with PHA or with PMA and ionomycin. In v ivo, NTT transcripts are found only in activated, but not resting, T c ells. Transcripts were absent in a variety of lymphoid cell lines and transformed lines from other tissues. NTT is a new member of the small group of genes including XIST (X(i)-specific transcript), H19, and IP W (imprinted gene in the Prader-Willi syndrome region), which are tran scribed but not translated, and may have a role in the regulation of n eighboring genes. XIST, H19, and IPW exhibit monoallelic expression, b ut both NTT alleles are expressed in CD4(+) T-cell clones. Southern bl ot and fluorescence in situ hybridization analyses show that NTT is a single-copy gene residing in chromosome 6q23-q24, near the interferon- gamma receptor gene (IFN-gamma). Their proximity and shared expression pattern suggest a possible functional relationship. (C) 1997 Academic Press