| Full text | |
| Author(s): Show less - |
Correa-Velloso, Juliana C.
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Linardi, Alessandra M.
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Glaser, Talita
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Velloso, Fernando J.
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Rivas, Maria P.
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Leite, Renata E. P.
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Grinberg, Lea T.
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Ulrich, Henning
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Akins, Michael R.
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Chiavegatto, Silvana
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Haddad, Luciana A.
Total Authors: 11
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| Document type: | Journal article |
| Source: | BMC NEUROSCIENCE; v. 23, n. 1, p. 15-pg., 2022-05-31. |
| Abstract | |
Background Fragile X syndrome, the major cause of inherited intellectual disability among men, is due to deficiency of the synaptic functional regulator FMR1 protein (FMRP), encoded by the FMRP translational regulator 1 (FMR1) gene. FMR1 alternative splicing produces distinct transcripts that may consequently impact FMRP functional roles. In transcripts without exon 14 the translational reading frame is shifted. For deepening current knowledge of the differential expression of Fmr1 exon 14 along the rat nervous system development, we conducted a descriptive study employing quantitative RT-PCR and BLAST of RNA-Seq datasets. Results We observed in the rat forebrain progressive decline of total Fmr1 mRNA from E11 to P112 albeit an elevation on P3; and exon-14 skipping in E17-E20 with downregulation of the resulting mRNA. We tested if the reduced detection of messages without exon 14 could be explained by nonsense-mediated mRNA decay (NMD) vulnerability, but knocking down UPF1, a major component of this pathway, did not increase their quantities. Conversely, it significantly decreased FMR1 mRNA having exon 13 joined with either exon 14 or exon 15 site A. Conclusions The forebrain in the third embryonic week of the rat development is a period with significant skipping of Fmr1 exon 14. This alternative splicing event chronologically precedes a reduction of total Fmr1 mRNA, suggesting that it may be part of combinatorial mechanisms downregulating the gene's expression in the late embryonic period. The decay of FMR1 mRNA without exon 14 should be mediated by a pathway different from NMD. Finally, we provide evidence of FMR1 mRNA stabilization by UPF1, likely depending on FMRP. (AU) | |
| FAPESP's process: | 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases |
| Grantee: | Alexander Henning Ulrich |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/06100-8 - Susceptibility and resilience to the effects of chronic psychosocial stress in adolescence: participation of the neuronal nitric oxide synthase (nNOS) |
| Grantee: | Silvana Chiavegatto |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 19/10868-4 - Expression analysis of FMR1 splicing products |
| Grantee: | Luciana Amaral Haddad |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 11/14329-9 - Functional analyses on FMRP isoforms displaying the long, variable loop of KH2 domain |
| Grantee: | Luciana Amaral Haddad |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 09/01333-8 - Chronic administration of 13-cis-retinoic acid (isotretinoin) in adolescent male mice: emotional behaviors and mRNA levels of several brain 5-HT receptors |
| Grantee: | Silvana Chiavegatto |
| Support Opportunities: | Regular Research Grants |