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An Eutherian-Specific microRNA Controls the Translation ofSatb2in a Model of Cortical Differentiation

Authors: Manuella Martins; Silvia Galfre`; Marco Terrigno; Luca Pandolfini; Irene Appolloni; Keagan Dunville; Andrea Marranci; +9 Authors

An Eutherian-Specific microRNA Controls the Translation ofSatb2in a Model of Cortical Differentiation

Abstract

ABSTRACTCerebral cortical development is controlled by key transcription factors that specify the neuronal identities in the different cortical layers. These transcription factors are crucial for the identity of the different neurons, but the mechanisms controlling their expression in distinct cells are only partially known. Here we investigate the expression and stability of the mRNAs of Tbr1, Bcl11b, Fezf2, Satb2 and Cux1 in single developing mouse cortical cells. We focus on Satb2 and find that its mRNA expression occurs much earlier than its protein synthesis and in a set of cells broader than expected, suggesting an initially tight control of its translation, which is subsequently de-repressed at late developmental stages. Mechanistically,Satb23’UTR modulates protein translation of GFP reporters during mouse corticogenesis. Byin vitropull-down ofSatb23’UTR-associated miRNAs, we select putative miRNAs responsible for SATB2 inhibition, focusing on those strongly expressed in early progenitor cells and reduced in late cells. miR-541, an Eutherian-specific miRNA, and miR-92a/b are the best candidates and their inactivation triggers robust and premature SATB2 translation in both mouse and human cortical cells. Our findings indicate that RNA interference plays a major role in the timing of cortical cell identity and may be part of the toolkit involved in specifying supra-granular projection neurons.

Country
Italy
Keywords

570, 571, in vitro corticogenesi, SATB2, cell fate, cell identity, corpus callosum, cortex, cortical layering, developmental timing, in vitro corticogenesis, mammalian evolution, miR-catch, microRNAs, neural stem cells, post-transcriptional control, Neurogenesis, 610, in&nbsp, post-transcriptional control, Article, Cell Line, corpus callosum, neural stem cell, Mice, SATB2; cell fate; cell identity; corpus callosum; cortex; cortical layering; developmental timing; in vitro corticogenesis; mammalian evolution; miR-catch; microRNA; neural stem cells; post-transcriptional control, cell fate; cell identity; corpus callosum; cortex; cortical layering; developmental timing; in vitro corticogenesis; mammalian evolution; microRNA; miR-catch; neural stem cells; post-transcriptional control; SATB2, SATB2, Animals, Humans, Developmental, developmental timing, 3' Untranslated Regions, neural stem cells, Cerebral Cortex, Settore BIO/11 - BIOLOGIA MOLECOLARE, cell fate, microRNA, Eutheria, cortical layering, Tumor Suppressor Proteins, miR-catch, Gene Expression Regulation, Developmental, Cell Differentiation, vitro corticogenesis, Matrix Attachment Region Binding Proteins, mammalian evolution, Repressor Proteins, MicroRNAs, cortex, Gene Expression Regulation, in vitro corticogenesis, cell identity, Cell fate; cell identity; corpus callosum; cortex; cortical layering; developmental timing; in vitro corticogenesis; mammalian evolution; microRNA; miR-catch; neural stem cells; post-transcriptional control; SATB2; 3' Untranslated Regions; Animals; Cell Differentiation; Cell Line; Cerebral Cortex; Eutheria; Gene Expression Regulation, Developmental; Humans; Matrix Attachment Region Binding Proteins; Mice; MicroRNAs; Neurogenesis; Repressor Proteins; Transcription Factors; Tumor Suppressor Proteins, Transcription Factors

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
13
Top 10%
Average
Top 10%
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gold