Evolutionary conservation of splice sites in sterile C mu transcripts and of immunoglobulin heavy chain (IgH) enhancer region sequences.
The immunoglobulin JHC mu intron was cloned from genomic DNA of a VHa3 rabbit and a 1257 bp sequence which contains conserved enhancer and splice sites was determined. From positions 315 to 1257, there is approximately 72 and 67% similarity to available sequences of man and mouse, respectively (counting gaps as single changes at single positions). In earlier studies of rabbit cDNAs encoding immunoglobulin heavy chains, we found a C mu-encoding cDNA clone (pB3) derived from splenic mRNA of a Trypanosome-hyperimmunized rabbit (VHa1) which lacked VH, DH or JH sequences and had an unknown sequence 5' of that encoding C mu. Comparison of this cDNA sequence with the present cloned genomic DNA sequence has now revealed that the start of cDNA pB3 corresponds to a position 80 base pairs 3' of the conserved octamer motif of the rabbit heavy chain enhancer. This mRNA was spliced to the acceptor site of C mu using a donor site which was 635 bp 3' of the enhancer octanucleotide. Our sequence of pB3 indicates that in rabbit as in mouse, a "nontron" (33 stop codons in three reading frames) can be formed utilizing a conserved splice site to produce a spliced transcript. The presence of evolutionarily conserved splice donor sites in the intron sequences of rabbit, mouse and man suggests a functional role during B cell ontogeny.
Mage
R G
RG
Laboratory of Immunology, NIAID, Bethesda, MD 20892.
Newman
B A
BA
Harindranath
N
N
Bernstein
K E
KE
Becker
R S
RS
Knight
K L
KL
D000818:Animals; D005075:Biological Evolution; D004247:DNA / Q000032:analysis; D004742:Enhancer Elements, Genetic; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D012326:RNA Splicing; D011817:Rabbits
D007143:Immunoglobulin Heavy Chains; D004247:DNA