Alternative polyadenylation (APA) produces mRNA isoforms with different 3UTR 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 3UTR 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 3UTR 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 3UTR 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 3UTR transcripts, implicating NXF1 as the nexus of gene expression regulation. SOURCE: Bin Tian (btian@rutgers.edu) -  Rutgers New Jersey Medical School

Pluto Bioinformatics

GSE117701: The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export