Cotranscription and intergenic splicing of human galactose-1-phosphate uridylyltransferase and interleukin-11 receptor α-chain genes generate a fusion mRNA in normal cells -: Implication for the production of multidomain proteins during evolution
Cotranscription and intergenic splicing of human galactose-1-phosphate uridylyltransferase and interleukin-11 receptor α-chain genes generate a fusion mRNA in normal cells -: Implication for the production of multidomain proteins during evolution
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DOI：
10.1074/jbc.273.26.16005
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发表时间：
1998-06-26
影响因子：
4.8
通讯作者：
Minvielle, S
中科院分区：
文献类型：
--
作者：
Magrangeas, F;Pitiot, G;Minvielle, S
在过去的十年中，人们的注意力主要集中在转录前起始复合物的形成作为调节基因表达的靶标上，而其他靶标（例如转录终止复合物组装）的研究较少。我们确定了正常人细胞中两个相邻基因（1-磷酸半乳糖尿苷酰转移酶 (GALT) 和白细胞介素 11 受体 α 链 (IL-11R α)）的 Poly(A) 位点选择和融合剪接的存在。这个 16 kb 的转录单元包含两个启动子（第一个是组成型的，第二个位于下游 8 kb，受到高度调控）和两个相距 12 kb 的切割/聚腺苷酸化信号。当第一个 Poly(A) 位点被剪接并且使用第二个聚（A），3-kb mRNA 编码功能未知的融合蛋白，包含部分 GALT 蛋白和整个 IL-11R α 蛋白。 GALT 启动子/IL-11R α Poly(A) 转录物是由泄漏终止和选择性剪接产生的。 RNA聚合酶（pol）II转录的这一特征与有效的RNA pol I和pol III终止相反，可能与染色体重排一起参与具有多个结构域的融合蛋白的生成，并且对于生成具有共同基序的新型蛋白质的自然过程具有重大的进化意义。我们的结果，连同基因组信息的积累，将激发基因表达研究中的新思考和实验。
In the past 10 years, much attention has been focused on transcription preinitiation complex formation as a target for regulating gene expression, and other targets such as transcription termination complex assemblage have been less intensively investigated. We established the existence of poly(A) site choice and fusion splicing of two adjacent genes, galactose-1-phosphate uridylyl-transferase (GALT) and interleukin-11 receptor alpha-chain (IL-11R alpha), in normal human cells. This 16-kilobase (kb) transcription unit contains two promoters (the first one is constitutive, and the second one, 8 kb downstream, is highly regulated) and two cleavage/polyadenylation signals separated by 12 kb, The promoter from the GALT gene yields two mRNAs, a 1,4-kb mRNA encoding GALT and a 3-kb fusion mRNA when the first poly(A) site is spliced out and the second poly(A) is used, The 3-kb mRNA codes for a fusion protein of unknown function, containing part of the GALT protein and the entire IL-11R alpha protein. The GALT promoter/IL-11R alpha poly(A) transcript results from leaky termination and alternative splicing. This feature of RNA polymerase (pol) II transcription, which contrasts with efficient RNA pol I and pol III termination, may be involved, together with chromosome rearrangements, in the generation of fusion proteins with multiple domains and would have major evolutionary implications in terms of natural processes to generate novel proteins with common motifs, Our results, together with accumulation of genomic informations, will stimulate new considerations and experiments in gene expression studies.