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免疫球蛋白重链基因的自发缺失:侧翼序列影响剪接位点选择。

Spontaneous deletions in Ig heavy chain genes: flanking sequences influence splice site selection.

作者信息

Ward S B, Morrison S L

机构信息

Department of Cellular and Molecular Biophysical Studies, Columbia University, New York, NY 10032.

出版信息

Nucleic Acids Res. 1991 Dec 11;19(23):6475-80. doi: 10.1093/nar/19.23.6475.

DOI:10.1093/nar/19.23.6475
PMID:1754385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC329201/
Abstract

The cell line G403.4.7, isolated as a spontaneous variant of the MPC-11 derived myeloma G403.4, produces a truncated gamma 2b HC protein, but no light chain (LC), and a single gamma 2b specific transcript of 2.4kb. This gamma 2b transcript consists of the VDJ and CH1 exons, the CH1 to Hinge (Hi) intervening sequence (IVS) and HI exon, part of the IVS between the two membrane exons M1 and M2, and most of the membrane 3' untranslated (UT) region. Even though the mature mRNA contains intronic sequences, it is abundant in the cytoplasm. Analysis of the gamma 2b genomic organization reveals that this unusual transcript results in part from two genomic deletions of 2.5kb and 588bp and in part from an altered splicing pattern. This altered splicing pattern is probably a consequence of the sequence alterations resulting from the genomic deletions. Analysis of these events provides some interesting insights into the mechanism of splice site selection and the evolution of introns and exons.

摘要

细胞系G403.4.7是从MPC - 11衍生的骨髓瘤G403.4自发变异而来,它产生一种截短的γ2b重链蛋白,但不产生轻链(LC),以及一个2.4kb的单一γ2b特异性转录本。这个γ2b转录本由VDJ和CH1外显子、CH1到铰链区(Hi)的间隔序列(IVS)和Hi外显子、两个膜外显子M1和M2之间IVS的一部分以及大部分膜3'非翻译(UT)区域组成。尽管成熟mRNA包含内含子序列,但它在细胞质中含量丰富。对γ2b基因组结构的分析表明,这种不寻常的转录本部分源于两个2.5kb和588bp的基因组缺失,部分源于改变的剪接模式。这种改变的剪接模式可能是基因组缺失导致的序列改变的结果。对这些事件的分析为剪接位点选择机制以及内含子和外显子的进化提供了一些有趣的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77f/329201/a46cf1d17908/nar00103-0121-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77f/329201/a46cf1d17908/nar00103-0121-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77f/329201/a46cf1d17908/nar00103-0121-a.jpg

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本文引用的文献

1
Organization of the rat gamma-fibrinogen gene: alternative mRNA splice patterns produce the gamma A and gamma B (gamma ') chains of fibrinogen.大鼠γ-纤维蛋白原基因的组织:可变mRNA剪接模式产生纤维蛋白原的γA和γB(γ')链。
Cell. 1982 Nov;31(1):159-66. doi: 10.1016/0092-8674(82)90415-9.
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Switch region of immunoglobulin Cmu gene is composed of simple tandem repetitive sequences.免疫球蛋白Cμ基因的转换区由简单串联重复序列组成。
Nature. 1981 Aug 27;292(5826):845-8. doi: 10.1038/292845a0.
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Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genes.
免疫球蛋白重链基因类别转换重组区域中的重复序列。
Cell. 1981 Feb;23(2):357-68. doi: 10.1016/0092-8674(81)90131-8.
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A gamma 2b-gamma 2a hybrid immunoglobulin heavy chain produced by a variant of the MPC 11 mouse myeloma cell line.由MPC 11小鼠骨髓瘤细胞系变体产生的γ2b-γ2a杂交免疫球蛋白重链。
Biochemistry. 1980 Apr 29;19(9):1730-7. doi: 10.1021/bi00550a002.
5
Mouse myeloma cells that make short immunoglobulin heavy chains: pleiotropic effects on glycosylation and chain assembly.产生短免疫球蛋白重链的小鼠骨髓瘤细胞:对糖基化和链组装的多效性影响
J Cell Biol. 1984 Jun;98(6):2215-21. doi: 10.1083/jcb.98.6.2215.
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Immunoglobulin gene transcription is activated by downstream sequence elements.免疫球蛋白基因转录由下游序列元件激活。
Cell. 1983 Jul;33(3):741-8. doi: 10.1016/0092-8674(83)90016-8.
7
Hybrid gamma 2b-gamma 2a genes expressed in myeloma variants: evidence for homologous recombination.在骨髓瘤变体中表达的杂交γ2b-γ2a基因:同源重组的证据。
Proc Natl Acad Sci U S A. 1983 Nov;80(22):6967-71. doi: 10.1073/pnas.80.22.6967.
8
Nucleotide sequences of gene segments encoding membrane domains of immunoglobulin gamma chains.编码免疫球蛋白γ链膜结构域的基因片段的核苷酸序列。
Proc Natl Acad Sci U S A. 1982 Apr;79(8):2623-7. doi: 10.1073/pnas.79.8.2623.
9
Isolation and characterization of a variant of mouse plasmacytoma J558 synthesizing a 110,000-dalton immunoglobulin heavy chain and of secondary variants synthesizing either a 55,000-dalton or an 80,000-dalton immunoglobulin heavy chain: possible implications.一种合成110,000道尔顿免疫球蛋白重链的小鼠浆细胞瘤J558变体以及合成55,000道尔顿或80,000道尔顿免疫球蛋白重链的二级变体的分离与鉴定:可能的意义
Mol Cell Biol. 1982 Sep;2(9):1134-44. doi: 10.1128/mcb.2.9.1134-1144.1982.
10
Loss of a consensus splice signal in a mutant immunoglobulin gene eliminates the CH1 domain exon from the mRNA.突变免疫球蛋白基因中共有剪接信号的缺失,使得mRNA中的CH1结构域外显子消失。
Mol Cell Biol. 1984 Jul;4(7):1270-7. doi: 10.1128/mcb.4.7.1270-1277.1984.