The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export

Alternative polyadenylation (APA) produces mRNA isoforms with different 3’UTR lengths. Previous studied indicated that 3’ end processing and mRNA nuclear export are intertwined in gene regulation. Here, we show that mRNA export factors generally facilitate usage of distal cleavage and polyadenylation sites (PASs), leading to expression of long 3’UTR isoforms. By focusing on the export receptor NXF1, which exhibits the most potent effect on APA in this study, we reveal a number of gene features that impact NXF1-dependent APA, including 3’UTR size, gene size and AT content. Surprisingly, downregulation of NXF1 results in accumulation of RNAP II at the 3’ end of genes, correlating with its role in APA regulation. Moreover, we show that NXF1 cooperates with CFI-68 to facilitate nuclear export of long 3’UTR isoform with UGUA motifs. Together, our work reveals several important roles of NXF1 in coordinating RNAPII distribution, 3’ end processing, and mRNA export of long 3’UTR transcripts, implicating NXF1 as the nexus of gene expression regulation. In total 9 3'READS libraries for analysis of APA under KD of export factors using total RNA from Hela cells. In total 8 3'READS libraries for analysis of APA under siNXF1 and siCFI-68 using cytoplasmic, monosomal fraction, and polysomal fraction from Hela cells. In total 4 ChIP-seq po2 IP and input libraries from HeLa cells for the analysis of po2 pausing under siNXF1. In total 2 ChATT-seq libraries from HeLa cells for the analysis of nasent RNA under siNXF1. In total 2 RNA-seq libraries from HeLa cells for the analysis of total RNA under siNXF1.