Parameters that govern the regulation of immunoglobulin delta heavy-chain gene expression.
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| Abstract |
The mu and delta immunoglobulin heavy-chain genes comprise a complex transcriptional unit in which a single mRNA precursor gives rise to mu- and delta-specific transcripts. During the immature B-cell stage, posttranscriptional processing events involving alternate splicing and cleavage-polyadenylation site selection give rise to mu- but not delta-encoding transcripts. In terminally differentiated B cells, delta mRNA is not synthesized because of a transcription termination event occurring upstream of the delta-gene locus. In an attempt to gain insight into the respective contributions of alternate splicing and cleavage-polyadenylation in the control of delta mRNA synthesis, we have constructed a set of plasmids in which membrane mu (mu m)-delta intergenic sequences containing the mu m poly(A) site but differing in splicing capacity were inserted in between a VH and delta gene. The mu m-delta insertion vectors were transfected into a B lymphoma line representative of an immature stage, and proximal mu m poly(A) site usage and delta mRNA synthesis were assessed. To determine unequivocally whether the mu m-delta intergenic region can regulate termination, the insertion vectors were also transfected into a B myeloma line, and transcription through the region was measured. In immature B-cell transfectants, splicing site selection was found to have a key role in determining poly(A) site utilization and concomitant delta mRNA expression. Mature delta mRNA synthesis was blocked by an upstream cleavage-polyadenylation event only when the proximal poly(A) site was associated with appropriate splicing signals. Furthermore, in vitro transcription assays revealed that the mu m-delta intergenic region is sufficient to regulate transcription termination within a 1,2430-base-pair region containing the mu m poly(A) site in myeloma transfectants. The mu m-delta insertion vectors provide an excellent model system for studying the regulatory aspects of this transcription termination event.
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| Authors | R Tisch, N Kondo, N Hozumi |
| Journal | Molecular and cellular biology (Mol Cell Biol) Vol. 10 Issue 10 Pg. 5340-8 (Oct 1990) ISSN: 0270-7306 [Print] United States |
| PMID | 2118995 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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