New ProteomeXchange dataset PXD072358

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Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:

https://proteomecentral.proteomexchange.org/dataset/PXD072358

Summary of dataset

Status: new
Identifier: PXD072358
HostingRepository: MassIVE
Species: Homo sapiens
Title: N6-adenosine methylation enhances nuclear mRNA export through METTL3 and NUP93
Submitter: Susan T. Weintraub
LabHead: Jihoon Lee
Description: Nuclear export of messenger RNAs (mRNAs) through nuclear pore complexes (NPCs) is a critical step in gene expression. Although N6-adenosine methylation (m6A) has been implicated in this process, the underlying mechanism remains obscure. Here, using single-molecule imaging, we demonstrate that m6A markedly accelerates nuclear export of messenger ribonucleoproteins (mRNPs) by increasing export efficiency and shortening export time through NPCs. We further show that the m6A methyltransferase METTL3 localizes at NPCs and functionally associates with the nucleoporin NUP93 to promote efficient export of m6A-modified mRNPs. Disruption of this functional association between METTL3 and NUP93 substantially impairs overall mRNP export efficiency. Notably, a steroid-resistant nephrotic syndrome (SRNS)-associated NUP93 variant (c.1162C>T, p.Arg388Trp) fails to associate with METTL3, resulting in defective nuclear export of key methylated mRNAs required for kidney function. Together,
our findings define an m6A-METTL3-NUP93 regulatory axis for nuclear mRNA export with broad implications for human disease.

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