Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla-Universidad Pablo de Olavide (CSIC-USE-UPO), Avenida Americo Vespucio, 41092, Seville, Spain.
Commun Biol. 2022 Mar 28;5(1):277. doi: 10.1038/s42003-022-03224-z.
Differential splicing efficiency of specific introns is a mechanism that dramatically increases protein diversity, based on selection of alternative exons for the final mature mRNA. However, it is unclear whether splicing efficiency of introns within the same gene is coordinated and eventually regulated as a mechanism to control mature mRNA levels. Based on nascent chromatin-associated RNA-sequencing data, we now find that co-transcriptional splicing (CTS) efficiency tends to be similar between the different introns of a gene. We establish that two well-differentiated strategies for CTS efficiency exist, at the extremes of a gradient: short genes that produce high levels of pre-mRNA undergo inefficient splicing, while long genes with relatively low levels of pre-mRNA have an efficient splicing. Notably, we observe that genes with efficient CTS display a higher level of mature mRNA relative to their pre-mRNA levels. Further, we show that the TGFβ signal transduction pathway regulates the general CTS efficiency, causing changes in mature mRNA levels. Taken together, our data indicate that CTS efficiency is a gene-specific characteristic that can be regulated to control gene expression.
特定内含子的差异剪接效率是一种基于对最终成熟 mRNA 中替代外显子的选择来极大增加蛋白质多样性的机制。然而，目前尚不清楚同一基因内内含子的剪接效率是否协调，并最终作为一种控制成熟 mRNA 水平的机制进行调节。基于新生染色质相关 RNA 测序数据，我们现在发现一个基因的不同内含子之间的共转录剪接（CTS）效率往往相似。我们确定了两种截然不同的 CTS 效率策略存在于一个梯度的两端：产生高水平前体 mRNA 的短基因经历低效剪接，而前体 mRNA 水平相对较低的长基因则具有高效剪接。值得注意的是，我们观察到具有高效 CTS 的基因相对于其前体 mRNA 水平表现出更高水平的成熟 mRNA。此外，我们还表明，TGFβ 信号转导途径调节一般 CTS 效率，导致成熟 mRNA 水平的变化。总之，我们的数据表明 CTS 效率是一种基因特异性特征，可以进行调节以控制基因表达。
