Guang Shouhong, Mertz Janet E
McArdle Laboratory for Cancer Research 1400 University Avenue University of Wisconsin Medical School Madison, WI 53706-1599, USA.
Nucleic Acids Res. 2005 Apr 20;33(7):2215-26. doi: 10.1093/nar/gki506. Print 2005.
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 beta-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 beta-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.
大多数编码mRNA的基因需要内含子才能在高等真核生物中高效表达。然而，如果mRNA含有顺式作用元件，如乙型肝炎病毒（HBV）的转录后调控元件（PRE）、马森 - 辉瑞猴病毒（MPMV）的组成型转运元件（CTE）或单纯疱疹病毒胸苷激酶（HSV - TK）基因的前体mRNA加工增强子（PPE），则它们无需切除内含子就能在细胞质中高效积累。我们比较了这些病毒元件、人类免疫缺陷病毒（HIV）的Rev反应元件（RRE）以及在此新鉴定的人类c - Jun基因增强子（CJE）的活性，以实现人类β - 珠蛋白基因无内含子变体的表达。来自天然无内含子基因的PRE、PPE和CJE，而不是来自含内含子基因的CTE或RRE，显著增强了稳定性、3'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仍然增强了mRNA的生物合成，在某些情况下无需切除内含子。因此，实现稳定性、3'端形成和核质转运的元件，而非内含子的存在或其本身的切除，对于mRNA生物合成是必需的。虽然CTE和RRE主要增强核质转运，但来自天然无内含子基因的PPE样元件也促进多聚腺苷酸化。
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