An intronic 10-base-pair deletion in a class II A beta gene affects RNA processing.
Several biologically important examples of posttranscriptionally regulated genes have recently been described (T. Gerster, D. Picard, and W. Schaffner, Cell 45:45-52, 1986; R. Reeves, T.S. Elton, M.S. Nissen, D. Lehn, and K.R. Johnson, Proc. Natl. Acad. Sci. USA 84:6531-6535, 1987; H.A. Young, L. Varesio, and P. Hwu, Mol. Cell. Biol. 6:2253-2256, 1986). Little is known, however, regarding sequences that mediate posttranscriptional RNA stability. Characterization in our laboratory of a mutant murine B lymphoma, M12.C3, revealed a posttranscriptional defect affecting the synthesis of a major histocompatibility complex class II gene (A beta d) whose product normally controls both the specificity and magnitude of the immune response. Molecular studies revealed that the mutation responsible for diminished A beta d gene expression was an intronic deletion of 10 base pairs (bp) located 99 bp 5' of the third exon. This deletion lies in a region not known to be critical for accurate and efficient splicing. Furthermore, sequence analysis of amplified A beta-specific cDNA demonstrated that the small number of A beta d transcripts produced in the mutant cells was correctly spliced. It appears that the mechanism by which this intronic 10-bp deletion acts to decrease RNA stability is unlikely to be at the level of RNA splicing.
Ghogawala
Z
Z
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts.
Choi
E
E
Daly
K R
KR
Blanco
L R
LR
Griffith
I J
IJ
Glimcher
L H
LH
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D003001:Cloning, Molecular; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007438:Introns / Q000502:physiology*; D008223:Lymphoma / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger