Maximal Efficacy of Alternative Splicing is Ensured by Balanced Efficiency of U1 and U2AF

Abstract Alternative splicing (AS) significantly increases the diversity of gene function by enabling a single gene to produce multiple protein isoforms. U1 and U2AF are proteins responsible for the recognition and splicing of an intron’s donor and acceptor sites, respectively. Here, we used RNA- seq to explore these fundamental splicing events to separately calculate the splicing efficiency of U1 and U2AF. The expression levels of splice sites were directly calculated by the number of uniquely mapped reads spanning the splice junction. We found that the scaled expression levels of donor and acceptor sites both follow a type III extreme value Weibull distribution with the same shape parameter of 0.14. These observations significantly extend our previous findings by revealing that AS follows a Weibull distribution at the levels of both the fundamental splicing event and the mature transcript isoform. A simple transform of the shape parameter a, 1/(1+a), ranges between 0 and 1, and positively correlates with the dominance of the major splicing product and therefore represents an index of the splicing machinery efficiency. Importantly, the equal splicing efficiency of U1 and U2AF ensure that their combined efficacy reaches a maximum. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵* Jianfei.hu{at}nih.gov (JH); ddouek{at}nih.gov (DCD) Corrected name error and removed line number