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It’s Not the Destination, It’s the Journey: Heterogeneity in mRNA Export Mechanisms

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The Biology of mRNA: Structure and Function

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1203))

Abstract

The process of creating a translation-competent mRNA is highly complex and involves numerous steps including transcription, splicing, addition of modifications, and, finally, export to the cytoplasm. Historically, much of the research on regulation of gene expression at the level of the mRNA has been focused on either the regulation of mRNA synthesis (transcription and splicing) or metabolism (translation and degradation). However, in recent years, the advent of new experimental techniques has revealed the export of mRNA to be a major node in the regulation of gene expression, and numerous large-scale and specific mRNA export pathways have been defined. In this chapter, we will begin by outlining the mechanism by which most mRNAs are homeostatically exported (“bulk mRNA export”), involving the recruitment of the NXF1/TAP export receptor by the Aly/REF and THOC5 components of the TREX complex. We will then examine various mechanisms by which this pathway may be controlled, modified, or bypassed in order to promote the export of subset(s) of cellular mRNAs, which include the use of metazoan-specific orthologs of bulk mRNA export factors, specific cis RNA motifs which recruit mRNA export machinery via specific trans-acting-binding factors, posttranscriptional mRNA modifications that act as “inducible” export cis elements, the use of the atypical mRNA export receptor, CRM1, and the manipulation or bypass of the nuclear pore itself. Finally, we will discuss major outstanding questions in the field of mRNA export heterogeneity and outline how cutting-edge experimental techniques are providing new insights into and tools for investigating the intriguing field of mRNA export heterogeneity.

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Acknowledgments

The authors thank Daniel Zenklusen for critical reading of the manuscript, as well as Eric Lécuyer and François Robert for comments on the manuscript during preparation. This work has been supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and Fonds de recherche du Québec—Santé (FRQ-S Chercheur-boursier Junior 2) for MO.

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Authors and Affiliations

  1. Institut de recherches cliniques de Montréal, Montréal, QC, Canada

    Daniel D. Scott, L. Carolina Aguilar, Mathew Kramar & Marlene Oeffinger

  2. Faculty of Medicine, Division of Experimental Medicine, McGill University, Montréal, QC, Canada

    Daniel D. Scott, Mathew Kramar & Marlene Oeffinger

  3. Faculté de Médecine, Département de Biochimie, Université de Montréal, Montréal, QC, Canada

    Marlene Oeffinger

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  1. Daniel D. Scott
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  2. L. Carolina Aguilar
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  3. Mathew Kramar
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  4. Marlene Oeffinger
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Correspondence to Marlene Oeffinger .

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Editors and Affiliations

  1. Systems biology (IRCM), Biochemistry and Molecular Medicine (UdeM), Experimental Medicine (McGill), Institut de recherches cliniques de Montréal (IRCM), Université de Montréal, McGill University, Montreal, QC, Canada

    Marlene Oeffinger

  2. Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC, Canada

    Daniel Zenklusen

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Scott, D.D., Aguilar, L.C., Kramar, M., Oeffinger, M. (2019). It’s Not the Destination, It’s the Journey: Heterogeneity in mRNA Export Mechanisms. In: Oeffinger, M., Zenklusen, D. (eds) The Biology of mRNA: Structure and Function . Advances in Experimental Medicine and Biology, vol 1203. Springer, Cham. https://doi.org/10.1007/978-3-030-31434-7_2

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