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Artimagnella, O.

Publications and source records attributed to Artimagnella, O..

2 recordsLinked to original sources

Foxg1 and companions: not only transcription factors

Here, moving from our most recent results on Foxg1 biology, we firstly summarize available information about a few, special pleiotropic effectors of neurodevelopmental interest, involved in control of both transcription and post-transcriptional steps of gene expression. Next, upon further scanning of literature, we report evidence that, not strictly limited to neurodevelopmental processes, such functional pleiotropy also applies to other transcription factors, involved in physiology and homeostasis. Besides, by systematic mining of a major public protein-protein interaction database, we collect robust evidence that an involvement of "canonical" transcription factors in post-transcriptional control of gene expression may be a pervasive phenomenon, characterizing hundreds of effectors. Finally, we discuss the biological meaning of these findings and propose three evolutionary mechanisms that may have conspired to such unexpected scenario.

molecular biology↗

Foxg1 regulates translation of neocortical neuronal genes, including the main NMDA receptor subunit gene, Grin1.

Mainly known as a transcription factor patterning the rostral brain and governing its histogenesis, Foxg1 has been also detected outside the nucleus, however biological meaning of that has been only partially clarified. Here, moving from Foxg1 expression in cytoplasm of neocortical neurons, we investigated its implication in translational control. We documented an impact of Foxg1 on ribosomal recruitment of Grin1-mRNA, encoding for the main subunit of NMDA receptor. Next, we showed that Foxg1 increases Grin1 protein level by enhancing translation of its mRNA, while not increasing its stability. Such enhancement was associated to augmented translational initiation and, possibly, polypeptide elongation. Molecular mechanisms at the basis of this activity included Foxg1 interaction with Eif4e and Eef1d as well as with Grin1-mRNA. Besides, we found that, within murine neocortical cultures, Grin1 de novo synthesis undergoes a prominent and reversible, homeostatic regulation and Foxg1 is instrumental to that. Finally, through TRAP-seq, we discovered that Foxg1 is implicated in the translation of hundreds of neuronal genes at the level of ribosome engagement and progression. All that points to Foxg1 as a key effector, crucial to multi-scale temporal tuning of neocortical pyramid activity, an issue with profound physiological and neuropathological implications.

molecular biology↗