Aksenova Vasilisa, Smith Alexandra, Lee Hangnoh, Bhat Prasanna, Esnault Caroline, Chen Shane, Iben James, Kaufhold Ross, Yau Ka Chun, Echeverria Carlos, Fontoura Beatriz, Arnaoutov Alexei, Dasso Mary
Division of Molecular and Cellular Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA.
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Nat Commun. 2020 Sep 11;11(1):4577. doi: 10.1038/s41467-020-18266-2.
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.
核孔复合体（NPCs）对于细胞功能而言至关重要，其作用不仅限于核质运输，还包括基因组组织和基因表达。NPCs的这种多面性以及其组成成分的缓慢更新，使得研究单个核孔蛋白如何在这些不同过程中发挥作用变得复杂。为了解决这个问题，我们应用了生长素诱导降解（AID）系统来区分篮状核孔蛋白NUP153、NUP50和TPR的作用。TPR的急性缺失会导致转录组图谱迅速发生显著变化。这些变化与NUP153或NUP50缺失后观察到的变化不同，但与mRNA输出受体NXF1或转录-输出-2（TREX-2）mRNA输出复合体的GANP亚基缺失所引起的变化密切相关。此外，TPR缺失会破坏TREX-2亚基（GANP、PCID2、ENY2）与NPCs的结合，并导致RNA转录和输出异常。我们的研究结果表明，TPR在通过TREX-2和/或NXF1依赖的mRNA周转进行基因表达过程中具有独特且关键的作用。
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