In eukaryotic cells, steady-state levels of mRNAs are determined by the regulated rates of a number of processes, including transcription, mRNA maturation, and mRNA degradation 1. Taken together, our data indicate that CTS efficiency is a gene-specific characteristic that can be regulated to control gene expression. Further, we show that the TGFβ signal transduction pathway regulates the general CTS efficiency, causing changes in mature mRNA levels. Notably, we observe that genes with efficient CTS display a higher level of mature mRNA relative to their pre-mRNA levels. 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. 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. ![]() ![]() ![]() 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. 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.
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