EXPRESSION OF NOVEL TRANSPOSON-CONTAINING MESSENGER-RNAS IN HUMAN T-CELLS

The HERV-H family of endogenous retrovirus like elements is the larges t such human family known. Using an HERV-H LTR probe, 6 and 4.5 kb tra nscripts were detected by Northern blot analysis which were induced in normal peripheral T cells after treatment with phytohaemaglutinin (PH A). Expression was not evident 30 min after treatment with phorbol est er, was increased within 3-4 h after treatment, reached a maximum afte r 8 h and then declined to low levels 24 h after treatment. Expression was inhibited totally by cycloheximide (10 mu M) and by the immunosup pressant cyclosporin A (1 mu g/ml). Using probes specific for the U3 a nd U5 regions of the HERV-H LTR, in combination with internal HERV-H p robes, evidence was obtained that the 6 and 4.5 kb transcripts are pol yadenylated from an HERV-H LTR. A cDNA library was constructed from T cells which had been treated with PHA for 8 h and a 1.7 kb clone was i solated using the HERV-H LTR probe. The insert contained a novel tande m array of an Alu, a LINE-1 element, two endogenous retroviral LTRs an d an A-T-rich sequence. The A-T-rich sequence contained multiple copie s of AUUUA mRNA regulatory motifs. Because of its high expression leve l, defined transcription kinetics, novel cassette-like composition and the presence of conserved mRNA stabilization sequences, we hypothesiz e that the transcript may play a biological role during T cell activat ion.