biostudies-literatureSanchez-Escabias EMinistry of Economy and Competitiveness | Agencia Estatal de InvestigaciónMinistry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)Consejería de Economía, Innovación, Ciencia y Empleo, Junta de AndalucíaConsejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (Ministry of Economy, Innovation, Science and Employment, Government of Andalucia)277https://www.ebi.ac.uk/biostudies/studies/S-EPMC8960766biostudies-literatureUnknown5(1)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 spliCommunications biologyCo-transcriptional splicing efficiency is a gene-specific feature that can be regulated by TGFβ.PMC8960766BFU2017-85420-RP18-FR-1962PID2020-118516GB-I00Reyes JCGuerrero-Martinez JASanchez-Escabias EfalseCo-transcriptional splicing efficiency is a gene-specific feature that can be regulated by TGFβ.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 spli2022-01-01T00:00:00Z2022 Mar2025-04-19T17:38:34.459Z2025-04-19T17:38:34.459ZS-EPMC89607663534722610.1038/s42003-022-03224-z