Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Fmr1 exon 14 skipping in late embryonic development of the rat forebrain
BMC neuroscience, v 23(1), pp 32-32
31 May 2022
PMID: 35641906
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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.
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.
Metrics
10 Record Views
Details
- Title
- Fmr1 exon 14 skipping in late embryonic development of the rat forebrain
- Creators
- Juliana C Corrêa-Velloso - Universidade de São PauloAlessandra M Linardi - Department of Genetics and Evolutionary Biology, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, 277 # 327, São Paulo, SP, 05508-090, BrazilTalita Glaser - Department of Biochemistry, Instituto de Química, Universidade de São Paulo, São Paulo, SP, BrazilFernando J Velloso - Department of Genetics and Evolutionary Biology, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, 277 # 327, São Paulo, SP, 05508-090, BrazilMaria P Rivas - Department of Genetics and Evolutionary Biology, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, 277 # 327, São Paulo, SP, 05508-090, BrazilRenata E P Leite - Department of Pathology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, BrazilLea T Grinberg - Department of Pathology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, BrazilHenning Ulrich - Department of Biochemistry, Instituto de Química, Universidade de São Paulo, São Paulo, SP, BrazilMichael R Akins - Drexel UniversitySilvana Chiavegatto - Department of Psychiatry, Instituto de Psiquiatria, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, BrazilLuciana A Haddad - Department of Genetics and Evolutionary Biology, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, 277 # 327, São Paulo, SP, 05508-090, Brazil. haddadL@usp.br
- Publication Details
- BMC neuroscience, v 23(1), pp 32-32
- Publisher
- Springer BMC
- Grant note
- 2017/06100-8 / Fundação de Amparo à Pesquisa do Estado de São Paulo 2009/01333-8 / Fundação de Amparo à Pesquisa do Estado de São Paulo 2008/53857-8 / Fundação de Amparo à Pesquisa do Estado de São Paulo 2019/10868-4 / Fundação de Amparo à Pesquisa do Estado de São Paulo 2018/07366-4 / Fundação de Amparo à Pesquisa do Estado de São Paulo 2011/14329-9 / Fundação de Amparo à Pesquisa do Estado de São Paulo 2009/51297-8 / Fundação de Amparo à Pesquisa do Estado de São Paulo 001 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000803888200001
- Scopus ID
- 2-s2.0-85130987340
- Other Identifier
- 991019168221704721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences