An intronic 10-base-pair deletion in a class II A beta gene affects RNA processing.
An intronic 10-base-pair deletion in a class II A beta gene affects RNA processing.
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II A 类 beta 基因中的内含子 10 个碱基对缺失会影响 RNA 加工。
DOI：
10.1128/mcb.9.10.4402-4408.1989
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发表时间：
1989
影响因子：
5.3
通讯作者：
Glimcher,LH
中科院分区：
文献类型：
--
作者：
Ghogawala,Z;Choi,E;Daly,KR;Blanco,LR;Griffith,IJ;Glimcher,LH
最近已经描述了转录后调节基因的几个生物学上重要的例子（T. Gerster，D. Picard和W. Schaffner，Cell 45：45- 52，1986; R. Reeves，T. S. Elton，M. S. Nissen，D. Lehn和K. R.约翰逊，Proc. Natl. Acad. Sci. USA 84：6531-6535，1987; H. A.扬湖，澳-地Varesio和P. Hwu，Mol. Cell. 6：2253-2256，1986）。然而，关于介导转录后RNA稳定性的序列知之甚少。我们实验室对突变型小鼠B淋巴瘤M12.C3的特征分析显示，转录后缺陷影响主要组织相容性复合物II类基因（Aβd）的合成，该基因产物通常控制免疫应答的特异性和强度。分子生物学研究表明，导致Aβ d基因表达降低的突变是位于第三外显子5′端99 bp处的10个碱基对（bp）的内含子缺失。这种缺失位于一个已知对准确和有效剪接不重要的区域。此外，对扩增的Aβ特异性cDNA的序列分析表明，突变细胞中产生的少量Aβ d转录本是正确剪接的。看来，这种内含子10-bp缺失降低RNA稳定性的机制不太可能是在RNA剪接水平上。
Several biologically important examples of posttranscriptionally regulated genes have recently been described (T. Gerster, D. Picard, and W. Schaffner, Cell 45:45-52,1986; R. Reeves, T. S. Elton, M. S. Nissen, D. Lehn, and K. R. Johnson, Proc. Natl. Acad. Sci. USA 84:6531-6535, 1987; H. A. Young, L. Varesio, and P. Hwu, Mol. Cell. Biol. 6:2253-2256, 1986). Little is known, however, regarding sequences that mediate posttranscriptional RNA stability. Characterization in our laboratory of a mutant murine B lymphoma, M12.C3, revealed a posttranscriptional defect affecting the synthesis of a major histocompatibility complex class II gene (Aβd) whose product normally controls both the specificity and magnitude of the immune response. Molecular studies revealed that the mutation responsible for diminished Aβdgene expression was an intronic deletion of 10 base pairs (bp) located 99 bp 5′ of the third exon. This deletion lies in a region not known to be critical for accurate and efficient splicing. Furthermore, sequence analysis of amplified Aβ-specific cDNA demonstrated that the small number of Aβdtranscripts produced in the mutant cells was correctly spliced. It appears that the mechanism by which this intronic 10-bp deletion acts to decrease RNA stability is unlikely to be at the level of RNA splicing.