Regulation of mRNA Export by Key Signaling Pathways and its Implications for Embryonic Stem Cell Differentiation and Potency: A Systematic Review

Objective: This study focuses on the regulatory role of mRNA export in embryonic stem cell (ESC) potency and differentiation, vital processes for developmental biology. It investigates how various signaling pathways influence mRNA export and their implications for regenerative medicine and cancer treatment. Background: Signaling pathways such as PI3K-Akt and MAPK/ERK are recognized for their roles in cell behavior; however, their influence on mRNA export regulation remains inadequately explored. A comprehensive understanding of these interactions could enhance the control of ESC differentiation and identify novel therapeutic targets for mitigating oncogene expression in cancer. Methods: A systematic review was conducted, utilizing databases including PubMed, MEDLINE, Google Scholar, and various open access/subscription journals, to gather pertinent articles on the regulation of mRNA export during embryonic development and its effects on ESC differentiation and potency. The literature search was unrestricted by publication date. Following specific criteria outlined in the methodology section, relevant studies were analyzed to shed light on the molecular mechanisms by which signaling pathways interact with the mRNA export machinery and their consequences for cell behavior and lineage-specific gene expression. The investigation adhered to PRISMA guidelines for systematic reviews. Results: The findings indicate that a range of signaling pathways—specifically, Nuclear Transport, PI3K-Akt, MAPK/ERK, Wnt/β-catenin, Notch, TGF-β, mTOR, p53, cAMP/PKA, and JNK—significantly regulate mRNA export throughout embryonic development. These pathways interact with export machinery components, such as NXF1 and TREX, and RNA-binding proteins like ALYREF, to modulate the export of mRNAs associated with pluripotency and differentiation. Notably, activation of pathways like PI3K-Akt and mTOR enhances the export of lineage-specific mRNAs, thereby promoting ESC differentiation, while inhibition of pathways such as JNK and p53 maintains pluripotency by decreasing differentiation-associated mRNA export. Conclusion: This investigation underscores the critical roles of key signaling pathways in regulating mRNA export during embryonic development. By influencing export machinery components, these pathways modulate ESC pluripotency and differentiation. Targeted manipulation of these pathways offers potential therapeutic strategies for advancing stem cell applications and regenerative medicine.