In the human genome, most genes undergo splicing, and patterns of codon usage are splicing dependent: guanine and cytosine (GC) content is the highest within single-exon genes and within first exons of multi-exon genes. However, the effects of codon usage on gene expression are typically characterized in unspliced model genes. Here, we measured the effects of splicing on expression in a panel of synonymous reporter genes that varied in nucleotide composition. We found that high GC content increased protein yield, mRNA yield, cytoplasmic mRNA localization, and translation of unspliced reporters. Splicing did not affect the expression of GC-rich variants. However, splicing promoted the expression of AT-rich variants by increasing their steady-state protein and mRNA levels, in part through promoting cytoplasmic localization of mRNA. We propose that splicing promotes the nuclear export of AU-rich mRNAs and that codon- and splicing-dependent effects on expression are under evolutionary pressure in the human genome.

在人类基因组中，大多数基因都经历剪接，并且密码子使用模式依赖于剪接：鸟嘌呤和胞嘧啶 (GC) 含量在单外显子基因和多外显子基因的第一个外显子中最高。然而，密码子使用对基因表达的影响通常以未剪接的模型基因为特征。在这里，我们在一组核苷酸组成不同的同义报告基因中测量了剪接对表达的影响。我们发现高 GC 含量增加了蛋白质产量、mRNA 产量、细胞质 mRNA 定位和未剪接记者的翻译。剪接不影响富含 GC 的变体的表达。然而，剪接通过增加其稳态蛋白质和mRNA水平来促进富含AT的变体的表达，部分通过促进mRNA的细胞质定位。