The genetic information encoded in nuclear mRNA destined to reach the cytoplasm requires the interaction of the mRNA molecule with the nuclear pore complex (NPC) for the process of mRNA export. Numerous proteins have important roles in the transport of mRNA out of the nucleus. The NPC embedded in the nuclear envelope is the port of exit for mRNA and is composed of ∼30 unique proteins, nucleoporins, forming the distinct structures of the nuclear basket, the pore channel and cytoplasmic filaments. Together, they serve as a rather stationary complex engaged in mRNA export, while a variety of soluble protein factors dynamically assemble on the mRNA and mediate the interactions of the mRNA with the NPC. mRNA export factors are recruited to and dissociate from the mRNA at the site of transcription on the gene, during the journey through the nucleoplasm and at the nuclear pore at the final stages of export. In this review, we present the current knowledge derived from biochemical, molecular, structural and imaging studies, to develop a high-resolution picture of the many events that culminate in the successful passage of the mRNA out of the nucleus.
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Cover Image
Cover Image
Left: In breast cancer cells TFEB (orange) is activated in the presence of doxorubicin, resulting in nuclear localization (top: vehicle treated, bottom: doxorubicin treated). Right: Knockdown of TFEB results in increased sensitivity to doxorubicin induced DNA damage as measured by H2A.X foci (yellow, top: vehicle treated, bottom: doxorubicin treated). Centre: In breast cancer, TFEB activation by DNA damage promotes expression of genes involved in apoptosis inhibition, DNA repair, and cell cycle regulation. Inhibition of TFEB causes increased DNA damage, interferon- and apoptosis signalling, leading to cell death. For more information see the article by Slade and colleagues on pp. 137–160. Image courtesy of Thomas Pulinilkunnil.
Into the basket and beyond: the journey of mRNA through the nuclear pore complex
Asaf Ashkenazy-Titelman, Yaron Shav-Tal, Ralph H. Kehlenbach; Into the basket and beyond: the journey of mRNA through the nuclear pore complex. Biochem J 17 January 2020; 477 (1): 23–44. doi: https://doi.org/10.1042/BCJ20190132
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