Distinct and opposite diversifying activities of terminal transferase splice variants.
The short splice variant of mouse terminal deoxynucleotidyl transferase (TdTS) catalyzes the addition of nontemplated nucleotides (N addition) at the coding joins of B cell and T cell antigen receptor genes. However, the activity and function of the long isoform of TdT (TdTL) have not been determined. We show here, in vitro and in vivo, that TdTL is a 3'-->5' exonuclease that catalyzes the deletion of nucleotides at coding joins. These findings suggest that the two TdT isoforms may act in concert to preserve the integrity of the variable region of antigen receptors while generating diversity.
Thai
To-Ha
TH
Division of Developmental and Clinical Immunology, Department of Microbiology, The University of Alabama at Birmingham, 35294, USA.
Purugganan
Mary M
MM
Roth
David B
DB
Kearney
John F
JF
D017398:Alternative Splicing / Q000276:immunology*; D020816:Amino Acid Motifs / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation / Q000276:immunology*; D001402:B-Lymphocytes / Q000201:enzymology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000737:chemistry; D004253:DNA Nucleotidylexotransferase / Q000235:genetics / Q000276:immunology*; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D007527:Isoenzymes; D012313:RNA; D004253:DNA Nucleotidylexotransferase