期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1988
卷号:85
期号:8
页码:2439-2443
DOI:10.1073/pnas.85.8.2439
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Alternative processing of the immunoglobulin mu primary transcript results in regulated production of mRNAs encoding the secreted (microseconds) and membrane-bound (micro m) form of IgM heavy chain during B-cell development. To elucidate the basis for this control, we analyzed the expression of altered forms of the mu transcription unit. Deletion of intron sequence between the microseconds and micro m exons, which reduces the distance between the two poly(A) sites as well as the distance between micro m splice sites, enhances production of micro m RNA. Correct expression is restored by insertion of heterologous sequences, demonstrating that spacing is indeed the critical aspect. The altered spacing appears to affect poly(A) site usage rather than splice site usage, since it was the distance between the poly(A) sites rather than the distance between splice sites that was found to be decisive. Finally, removal of either the C mu 4 splice donor or the m1 splice acceptor, thus eliminating normal micro m splicing, does not increase usage of the microseconds poly(A) site. We therefore conclude that the major factor in determining the ratio of microseconds to micro m is a poly(A) site choice rather than a splicing choice.