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 studies indicated that 3' end processing and mRNA 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 long 3' UTR isoform expression. By focusing on the export receptor NXF1, which exhibits the most potent effect on APA in this study, we reveal several gene features that impact NXF1-dependent APA, including 3' UTR size, gene size, and AT content. Surprisingly, NXF1 downregulation results in RNA polymerase II (Pol II) accumulation at the 3' end of genes, correlating with its role in APA regulation. Moreover, NXF1 cooperates with CFI-68 to facilitate nuclear export of long 3' UTR isoform with UGUA motifs. Together, our work reveals important roles of NXF1 in coordinating transcriptional dynamics, 3' end processing, and nuclear export of long 3' UTR transcripts, implicating NXF1 as a nexus of gene regulation.
['Chen|Suli|S|', 'Wang|Ruijia|R|', 'Zheng|Dinghai|D|', 'Zhang|Heng|H|', 'Chang|Xingya|X|', 'Wang|Ke|K|', 'Li|Wencheng|W|', 'Fan|Jing|J|', 'Tian|Bin|B|', 'Cheng|Hong|H|']
D020413:3' Untranslated Regions D021581:Active Transport, Cell Nucleus D001665:Binding Sites D002467:Cell Nucleus D057809:HEK293 Cells D006367:HeLa Cells D006801:Humans D007700:Kinetics D029543:Nucleocytoplasmic Transport Proteins D026723:Polyadenylation D011485:Protein Binding D012319:RNA Polymerase II D012333:RNA, Messenger D016601:RNA-Binding Proteins D014158:Transcription, Genetic
mRNA export NXF1 transcriptional dynamics alternative polyadenylation gene size AT content CFI-68 3′ UTR length TREX