首页> 美国卫生研究院文献>Nucleic Acids Research >Pre-mRNA processing enhancer (PPE) elements from intronless genes play additional roles in mRNA biogenesis than do ones from intron-containing genes
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Pre-mRNA processing enhancer (PPE) elements from intronless genes play additional roles in mRNA biogenesis than do ones from intron-containing genes

机译:与不含内含子的基因相比无内含子基因的mRNA前加工增强子(PPE)元素在mRNA生物发生中起着其他作用

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摘要

Most mRNA-encoding genes require introns for efficient expression in high eukaryotes. However, mRNAs can efficiently accumulate in the cytoplasm without intron excision if they contain cis-acting elements such as the post-transcriptional regulatory element (PRE) of hepatitis B virus (HBV), the constitutive transport element (CTE) of Mason–Pfizer monkey virus (MPMV), or the pre-mRNA processing enhancer (PPE) of herpes simplex virus' thymidine kinase (HSV-TK) gene. We compared the activities of these viral elements, the Rev-responsive element (RRE) of the human immunodeficiency virus (HIV), and the human c-Jun gene's enhancer (CJE), an element newly identified here, to enable expression of an intronless variant of the human β-globin gene. The PRE, PPE and CJE from naturally intronless genes, but not the CTE or RRE from intron-containing genes, significantly enhanced stability, 3′ end processing and cytoplasmic accumulation. When the transcripts included the β-globin gene's first intron, the PRE, PPE and CJE still enhanced mRNA biogenesis, in some cases without intron excision. Thus, elements enabling stability, 3′ end formation and nucleocytoplasmic export, not the presence of introns or their excision per se, are necessary for mRNA biogenesis. While the CTE and RRE primarily enhance nucleocytoplasmic export, PPE-like elements from naturally intronless genes facilitate polyadenylation as well.
机译:大多数mRNA编码基因需要内含子才能在高等真核生物中有效表达。但是,如果mRNA含有顺式作用元件,例如乙型肝炎病毒(HBV)的转录后调控元件(PRE),梅森-辉瑞猴的组成型转运元件(CTE),则它们可以有效地在细胞质中蓄积而无需内含子切除。病毒(MPMV)或单纯疱疹病毒胸苷激酶(HSV-TK)基因的mRNA前加工增强子(PPE)。我们比较了这些病毒成分,人类免疫缺陷病毒(HIV)的Rev响应元件(RRE)和人类c-Jun基因增强子(CJE)(在此新鉴定的一种元件)的活性,以使其能够表达无内含子β-珠蛋白基因的变异体。来自天然无内含子基因的PRE,PPE和CJE,而非来自含内含子基因的CTE或RRE,显着增强了稳定性,3'末端加工和细胞质积累。当转录本包含β-珠蛋白基因的第一个内含子时,PRE,PPE和CJE仍会增强mRNA的生物发生,在某些情况下无需内含子切除。因此,实现稳定,3'端形成和核质输出的元件,而不是内含子的存在或其本身的切除,对于mRNA生物发生而言是必需的。尽管CTE和RRE主要增强了核质的输出,但是来自天然无内含子基因的PPE样元件也促进了聚腺苷酸化。

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