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Unappreciated Role of mRNA Export Receptor NXF1: a Nexus to Streamline Gene Expression
 
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In eukaryotes, expression of protein-coding genes is a complex process that involves transcription, processing of the nascent transcripts, nuclear export, and translation. Distinct steps are often coupled to one another to ensure streamlined regulation. mRNA export is a key step of gene regulation that requires the transport receptor, a heterodimer of NXF1-NXT1.
The 3' end of almost all eukaryotic mRNAs is polyadenylated. Most eukaryotic genes contain multiple polyadenylation sites (PASs), leading to alternative polyadenylation (APA), which has been increasingly appreciated as an important layer of post-transcriptional regulation. Multiple lines of evidence indicates that 3' end processing and nuclear export are interconnected. However, how mRNA export factors in general regulates APA and how nuclear export of APA isoforms are controlled to precisely regulate gene expression remain unknown.
In a recently study published in Molecular Cell, scientists from Shanghai Institute of Biochemistry and Cell Biology of Chinese Academy of Sciences and Rutgers New Jersey Medical School reported that mRNA export receptor NXF1 coordinates transcriptional dynamics, APA, and mRNA export.
They found that mRNA export factors generally promote distal PAS usage, leading to expression of long 3' UTR isoforms.
Focusing on the export receptor NXF1, they revealed novel gene features that govern APA regulation, including gene size and nucleotide content.
Using ChIP-seq and nascent RNA-seq, they showed that NXF1 regulates RNA polymerase II (RNAP II) distribution along the gene and transcription dynamics at the 3' end, correlating with its role in regulation of PAS choice. Moreover, they found that NXF1 interacts with the 3' processing factor CFI-68 to promote nuclear export of long 3' UTR isoforms.
This study revealed a previously unappreciated role of NXF1 as a nexus to coordinates transcription dynamics, APA and nuclear export to streamline gene expression. It sets an example of how a RNA-binding protein ensures effective and precise gene expression through coordinating multiple processes in the gene expression pathway.
                                                                                                                                     
Reference: https://www.cell.com/molecular-cell/fulltext/S1097-2765(19)30046-2

 

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