The mRNA Export Receptor NXF1 Coordinates Transcriptional Dynamics, Alternative Polyadenylation, and mRNA Export

Molecular Cell
Suli ChenHong Cheng

Abstract

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.

Citations

Nov 16, 2019·Science·Sandra L Wolin, Lynne E Maquat
Apr 28, 2020·Emerging Topics in Life Sciences·Alexander M IshovJörg Bungert
Sep 29, 2020·Nucleic Acids Research·Jackson B TrotmanJ Mauro Calabrese
Jan 9, 2020·The Biochemical Journal·Asaf Ashkenazy-TitelmanRalph H Kehlenbach
Oct 22, 2020·Nature Reviews. Cancer·Gregory J Goodall, Vihandha O Wickramasinghe
Nov 10, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Alexander F Palazzo, Yoon Mo Kang
Dec 8, 2020·Essays in Biochemistry·Zhe Wu
Apr 13, 2021·Wiley Interdisciplinary Reviews. RNA·Isabel Pereira-Castro, Alexandra Moreira
May 1, 2021·International Journal of Molecular Sciences·Baojin Ding, Masood Sepehrimanesh
Jul 21, 2021·Biochemical Society Transactions·Alexandr A MakarovMark C Field
Sep 29, 2021·Wiley Interdisciplinary Reviews. RNA·Neeraja K MohananRakesh S Laishram
Oct 14, 2021·Biochemical Society Transactions·Sheng WangYang Yu
Oct 28, 2021·PLoS Pathogens·Daniel HeinzerAdriano Aguzzi

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