Distinct and opposite activities of human terminal deoxynucleotidyltransferase splice variants.
Evidence for potential human TdT (hTdT) isoforms derived from hTdT genomic sequences led us to identify the short isoform (hTdTS), as well as mature long transcripts containing exon XII (hTdTL1) and another including exon VII (hTdTL2) in lymphoid cells. Normal B and T lymphocytes express exclusively hTdTS and hTdTL2, whereas hTdTL1 expression appears to be restricted to transformed lymphoid cell lines. In in vitro recombination and primer assays, both long isoforms were shown to have 3'-->5' exonuclease activity. Overexpression of hTdTS or hTdTL2 greatly reduced the efficiency of recombination, which was reverted to normal levels by the simultaneous expression of both enzymes. Therefore, alternative splicing may prevent the adverse effects of unchecked elongation or diminution of coding ends during V(D)J recombination, thus affecting the survival of a B or T cell precursor during receptor gene rearrangements. Finally, the newly discovered hTdT isoforms should be considered in future screening of human leukemias.
Thai
To-Ha
TH
Division of Developmental and Clinical Immunology, University of Alabama, Birmingham 35294, USA.
Kearney
John F
JF
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004253:DNA Nucleotidylexotransferase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D016364:Reading Frames / Q000276:immunology; D011995:Recombination, Genetic / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D004277:DNA, Single-Stranded; D007527:Isoenzymes; D004247:DNA; D004253:DNA Nucleotidylexotransferase