Regulation of APOBEC3 gene expression and its transcript splicing

小鼠APOBEC3(MA3)基因座的多态与感染小鼠白血病病毒的易感性不同。在耐病毒的C57BL/6(B6)小鼠中，MA3的转录本和蛋白比敏感的BALB/c小鼠更丰富，并且这些品系的小鼠也表达不同剪接模式的MA3转录本。B6小鼠主要表达外显子5缺陷的转录本，这提供了比全长转录本更有效的翻译。通过利用基因组DNA克隆进行体外剪接分析，我们发现了调节MA3转录本中包含外显子5的两个关键决定因素：外显子5上游的TCCT重复数和新发现的外显子5内位于外显子5/内含子5边界上游12个碱基的单核苷酸多态。

Polymorphisms at the mouse APOBEC3(mA3) gene locus have been associated with different susceptibilities to infection with mouse leukemia viruses. In virus-resistant C57BL/6(B6) mice, mA3 transcripts and protein are more abundant than those in susceptible BALB/c mice, and these strains of mice also express mA3 transcripts with different splicing patterns. B6 mice express predominantly the exon 5-deficient transcript, which confer more efficient translation than the full-length transcript. By employing in vitro splicing assays using genomic DNA clones, we identified two critical determinants that regulate exon 5 inclusion into mA3 transcripts : the number of TCCT repeats upstream of exon 5 and the newly identified single nucleotide polymorphism within exon 5 located 12 bases upstream of the exon 5/intron 5 boundary.