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EnglishAlternative polyadenylation (APA) is a widespread mechanism involving about half of the expressed genes, resulting in varying lengths of the 3 ′ untranslated region (3 ′ UTR). Variations in length and sequence of the 3 ′ UTR may underlie changes of post-transcriptional processing, localization, miRNA targeting and stability of mRNAs. During embryonic development a large array of mRNAs exhibit APA, with a prevalence of the longer 3 ′ UTR versions in differentiating cells. Little is known about polyA+ site usage during differentiation of mammalian neural progenitors. Here we exploit a model of adherent neural stem (ANS) cells, which homogeneously and efficiently differentiate into GABAergic neurons. RNAseq data shows a global trend towards lengthening of the 3 ′ UTRs during differentiation. Enriched expression of the longer 3 ′ UTR variants of Pes1 and Gng2 was detected in the mouse brain in areas of cortical and subcortical neuronal differentiation, respectively, by two-probes fluorescent in situ hybridization (FISH). Among the coding genes upregulated during differentiation of ANS cells we found Elavl3, a neural-specific RNA-binding protein homologous to Drosophila Elav. In the insect, Elav regulates polyA+ site choice while interacting with paused Pol-II promoters. We tested the role of Elavl3 in ANS cells, by silencing Elavl3 and observed consistent changes in 3 ′ UTR length and delayed neuronal differentiation. These results indicate that choice of the polyA+ site and lengthening of 3 ′ UTRs is a possible additional mechanism of posttranscriptional RNA modification involved in neuronal differentiation.
| Titolo: | Choice of alternative polyadenylation sites, mediated by the rna-binding protein Elavl3, plays a role in differentiation of inhibitory neuronal progenitors |
| Autori Riconosciuti: | |
| Autori: | Grassi E.; Santoro R.; Umbach A.; Grosso A.; Oliviero S.; Neri F.; Conti L.; Ala U.; Provero P.; Dicunto F.; Merlo G.R. |
| Data di pubblicazione: | 2019 |
| Abstract: | Alternative polyadenylation (APA) is a widespread mechanism involving about half of the expressed genes, resulting in varying lengths of the 3 ′ untranslated region (3 ′ UTR). Variations in length and sequence of the 3 ′ UTR may underlie changes of post-transcriptional processing, localization, miRNA targeting and stability of mRNAs. During embryonic development a large array of mRNAs exhibit APA, with a prevalence of the longer 3 ′ UTR versions in differentiating cells. Little is known about polyA+ site usage during differentiation of mammalian neural progenitors. Here we exploit a model of adherent neural stem (ANS) cells, which homogeneously and efficiently differentiate into GABAergic neurons. RNAseq data shows a global trend towards lengthening of the 3 ′ UTRs during differentiation. Enriched expression of the longer 3 ′ UTR variants of Pes1 and Gng2 was detected in the mouse brain in areas of cortical and subcortical neuronal differentiation, respectively, by two-probes fluorescent in situ hybridization (FISH). Among the coding genes upregulated during differentiation of ANS cells we found Elavl3, a neural-specific RNA-binding protein homologous to Drosophila Elav. In the insect, Elav regulates polyA+ site choice while interacting with paused Pol-II promoters. We tested the role of Elavl3 in ANS cells, by silencing Elavl3 and observed consistent changes in 3 ′ UTR length and delayed neuronal differentiation. These results indicate that choice of the polyA+ site and lengthening of 3 ′ UTRs is a possible additional mechanism of posttranscriptional RNA modification involved in neuronal differentiation. |
| Volume: | 12 |
| Fascicolo: | 518 |
| Pagina iniziale: | 1 |
| Pagina finale: | 15 |
| Digital Object Identifier (DOI): | 10.3389/fncel.2018.00518 |
| URL: | https://www.frontiersin.org/articles/10.3389/fncel.2018.00518/pdf |
| Parole Chiave: | Elavl3; GABAergic; Neuron differentiation; Polyadenylation; RNA binding protein |
| Rivista: | FRONTIERS IN CELLULAR NEUROSCIENCE |
| Appare nelle tipologie: | 03A-Articolo su Rivista |
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