mRNA export and cancer

Abstract

Studies in the past several years highlight important features of the messenger RNA (mRNA) export process. For instance, groups of mRNAs acting in the same biochemical processes can be retained or exported in a coordinated manner thereby impacting on specific biochemistries and ultimately on cell physiology. mRNAs can be transported by either bulk export pathways involving NXF1/TAP or more specialized pathways involving chromosome region maintenance 1 (CRM1). Studies on primary tumor specimens indicate that many common and specialized mRNA export factors are dysregulated in cancer including CRM1, eukaryotic translation initiation factor 4E (eIF4E), HuR, nucleoporin 88, REF/Aly, and THO. This positions these pathways as potential therapeutic targets. Recently, specific targeting of the eIF4E-dependent mRNA export pathway in a phase II proof-of-principle trial with ribavirin led to impaired eIF4E-dependent mRNA export correlating with clinical responses including remissions in leukemia patients. Here, we provide an overview of these mRNA export pathways and highlight their relationship to cancer.