Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway

Vasilisa Aksenova, Alexandra Smith, Hangnoh Lee, Prasanna Bhat, Caroline Esnault, Shane Chen, James Iben, Ross Kaufhold, Ka Chun Yau, Carlos Echeverria, Beatriz Fontoura, Alexei Arnaoutov and Mary Dasso ()
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Vasilisa Aksenova: National Institute of Child Health and Human Development, National Institutes of Health
Alexandra Smith: National Institute of Child Health and Human Development, National Institutes of Health
Hangnoh Lee: National Institute of Child Health and Human Development, National Institutes of Health
Prasanna Bhat: University of Texas Southwestern Medical Center
Caroline Esnault: National Institute of Child Health and Human Development, National Institutes of Health
Shane Chen: National Institute of Child Health and Human Development, National Institutes of Health
James Iben: National Institute of Child Health and Human Development, National Institutes of Health
Ross Kaufhold: National Institute of Child Health and Human Development, National Institutes of Health
Ka Chun Yau: National Institute of Child Health and Human Development, National Institutes of Health
Carlos Echeverria: National Institute of Child Health and Human Development, National Institutes of Health
Beatriz Fontoura: University of Texas Southwestern Medical Center
Alexei Arnaoutov: National Institute of Child Health and Human Development, National Institutes of Health
Mary Dasso: National Institute of Child Health and Human Development, National Institutes of Health

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocytoplasmic trafficking, including genome organization and gene expression. This multi-faceted nature and the slow turnover of NPC components complicates investigations of how individual nucleoporins act in these diverse processes. To address this question, we apply an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins NUP153, NUP50 and TPR. Acute depletion of TPR causes rapid and pronounced changes in transcriptomic profiles. These changes are dissimilar to shifts observed after loss of NUP153 or NUP50, but closely related to changes caused by depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, TPR depletion disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) to NPCs and results in abnormal RNA transcription and export. Our findings demonstrate a unique and pivotal role of TPR in gene expression through TREX-2- and/or NXF1-dependent mRNA turnover.

Date: 2020
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DOI: 10.1038/s41467-020-18266-2

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