Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States.
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle, United States.
Elife. 2017 Dec 27;6:e32537. doi: 10.7554/eLife.32537.
Production of most eukaryotic mRNAs requires splicing of introns from pre-mRNA. The splicing reaction requires definition of splice sites, which are initially recognized in either intron-spanning ('intron definition') or exon-spanning ('exon definition') pairs. To understand how exon and intron length and splice site recognition mode impact splicing, we measured splicing rates genome-wide in , using metabolic labeling/RNA sequencing and new mathematical models to estimate rates. We found that the modal intron length range of 60-70 nt represents a local maximum of splicing rates, but that much longer exon-defined introns are spliced even faster and more accurately. We observed unexpectedly low variation in splicing rates across introns in the same gene, suggesting the presence of gene-level influences, and we identified multiple gene level variables associated with splicing rate. Together our data suggest that developmental and stress response genes may have preferentially evolved exon definition in order to enhance the rate or accuracy of splicing.
真核生物的大多数 mRNA 的产生都需要从前体 mRNA 中剪接内含子。剪接反应需要定义剪接位点，这些剪接位点最初是在内含子跨越（“内含子定义”）或外显子跨越（“外显子定义”）对中识别的。为了了解外显子和内含子长度以及剪接位点识别模式如何影响剪接，我们使用代谢标记/RNaseq 和新的数学模型在 中测量了全基因组范围内的剪接率，以估计速率。我们发现，60-70nt 的模式内含子长度范围代表剪接率的局部最大值，但即使是更长的外显子定义的内含子也能更快、更准确地进行剪接。我们观察到同一基因中剪接率在不同内含子之间的变化出乎意料地低，这表明存在基因水平的影响，我们还确定了与剪接率相关的多个基因水平变量。总之，我们的数据表明，发育和应激反应基因可能优先进化出外显子定义，以提高剪接的速度或准确性。
