C mu-containing transcripts initiate heterogeneously within the IgH enhancer region and contain a novel 5'-nontranslatable exon
- PMID: 3934561
- DOI: 10.1038/318475a0
C mu-containing transcripts initiate heterogeneously within the IgH enhancer region and contain a novel 5'-nontranslatable exon
Abstract
Transcriptional competence of the immunoglobulin heavy-chain locus (IgH) is established at an early stage of lymphoid cell development, leading to the appearance of RNA components, previously called C mu RNA1 or sterile-mu RNA2, which contain constant-region sequences but lack variable-region sequences. These components are of two types: those which initiate in the D region of alleles that have undergone DJH (diversity-joining region) rearrangement (D mu transcripts) and those which initiate within the JH-C mu intron (hereafter termed I mu transcripts). In pre-B and early B cells, D mu and I mu transcripts are nearly as abundant as the messenger RNA encoding mu heavy chain. The D mu transcripts are spliced into RNAs containing D, JH and C mu sequences, and in some, but not all, cases these RNAs are translated into D mu proteins. To establish whether the I mu transcripts have any translational potential and to elucidate the structure of their promoter region, we have determined their transcription initiation sites and their mode of splicing. As reported here, by using sequence analysis of cloned I mu complementary DNAs, primer extension and S1 nuclease mapping, we have found that these transcripts have remarkable 5' heterogeneity: there are more than five distinct start sites spanning a region of 44 nucleotides that is located downstream of an octanucleotide found in all variable-region promoters. Such imprecise initiation may result from the lack of a well-defined TATAA motif and the unusual proximity of the octanucleotide to the enhancer region. Approximately 700 nucleotides downstream from these initiation sites, a cryptic splice site is used to create a nontranslatable exon ('nontron') which is joined to the C mu 1 domain. The properties of the nontron may be important for the mechanism of allelic exclusion.
Similar articles
-
Evolutionary conservation of splice sites in sterile C mu transcripts and of immunoglobulin heavy chain (IgH) enhancer region sequences.Mol Immunol. 1989 Oct;26(10):1007-10. doi: 10.1016/0161-5890(89)90119-3. Mol Immunol. 1989. PMID: 2512480
-
Coordination of immunoglobulin DJH transcription and D-to-JH rearrangement by promoter-enhancer approximation.Mol Cell Biol. 1991 Apr;11(4):2096-107. doi: 10.1128/mcb.11.4.2096-2107.1991. Mol Cell Biol. 1991. PMID: 1900920 Free PMC article.
-
Transcripts of the immunoglobulin C mu gene vary in structure and splicing during lymphoid development.Proc Natl Acad Sci U S A. 1980 Dec;77(12):7400-4. doi: 10.1073/pnas.77.12.7400. Proc Natl Acad Sci U S A. 1980. PMID: 6784123 Free PMC article.
-
Immunoglobulin heavy chain enhancer is located near or in an initiation zone of chromosomal DNA replication.Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3695-9. doi: 10.1073/pnas.90.8.3695. Proc Natl Acad Sci U S A. 1993. PMID: 8475117 Free PMC article.
-
Normal isotype switching in B cells lacking the I mu exon splice donor site: evidence for multiple I mu-like germline transcripts.J Immunol. 2000 Feb 1;164(3):1451-7. doi: 10.4049/jimmunol.164.3.1451. J Immunol. 2000. PMID: 10640761
Cited by
-
Separate elements control DJ and VDJ rearrangement in a transgenic recombination substrate.EMBO J. 1990 Jan;9(1):117-25. doi: 10.1002/j.1460-2075.1990.tb08087.x. EMBO J. 1990. PMID: 2153073 Free PMC article.
-
Diversity of the mouse T cell receptor C gamma 1 gene: structural analysis in C57BL/Ka.Immunogenetics. 1988;27(2):121-6. doi: 10.1007/BF00351085. Immunogenetics. 1988. PMID: 2891611
-
Deletional rearrangement in the human T-cell receptor alpha-chain locus.Proc Natl Acad Sci U S A. 1987 Dec;84(23):8608-12. doi: 10.1073/pnas.84.23.8608. Proc Natl Acad Sci U S A. 1987. PMID: 3500476 Free PMC article.
-
Immunoglobulin heavy-chain switching may be directed by prior induction of transcripts from constant-region genes.Proc Natl Acad Sci U S A. 1988 Oct;85(20):7704-8. doi: 10.1073/pnas.85.20.7704. Proc Natl Acad Sci U S A. 1988. PMID: 2459714 Free PMC article.
-
Evolution of antibody class switching: identification and transcriptional control of an Inu exon in the duck (Anas platyrhynchos).Dev Comp Immunol. 2006;30(6):575-87. doi: 10.1016/j.dci.2005.05.004. Epub 2005 Jun 20. Dev Comp Immunol. 2006. PMID: 16480768 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials