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Research article
Fenghua Lan
Xiamen University Medical College
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2812-7145
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Genomic Data.
Background: the disease gene of fragile X syndrome, FMR1 gene, encodes fragile X mental retardation protein (FMRP). The alternative splicing (AS) of FMR1 can affect the structure and function of FMRP. However, the biological functions of alternatively spliced isoforms remain elusive. In a previous study, we identified a new 140 bp exon from the intron 9 of human FMR1 gene. In this study, we further examined the biological functions of this new exon and its underlying signaling pathways.
Results: qRT-PCR results showed that this novel exon is commonly expressed in the peripheral blood of normal individuals. Comparative genomics showed that sequences paralogous to the 140 bp sequence only exist in the genomes of primates. To explore the biological functions of the new transcript, we constructed recombinant eukaryotic expression vectors and lentiviral overexpression vectors. Results showed that the spliced transcript encoded a truncated protein which was expressed mainly in the cell nucleus. Additionally, several genes, including the BEX1 gene involved in mGluR-LTP or mGluR-LTD signaling pathways were significantly influenced when the truncated FMRP was overexpressed.
Conclusions: our work identified a new exon from amid intron 9 of human FMR1 gene with wide expression in normal healthy individuals, which emphasizes the notion that the AS of FMR1 gene is complex and may in a large part account for the multiple functions of FMRP.
Keywords
FMR1, FMRP, FXS, alternative splicing, alternative exon
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Peer Review Timeline
CURRENT STATUS: Published
Version 3
Posted 12 Jun, 2020
No comments provided
Editorial decision: Minor revision
On 23 May, 2020
Reviewer #2 agreed
On 18 May, 2020
Review #2 received
Received 18 May, 2020
Reviewer #1 agreed
On 16 May, 2020
Review #1 received
Received 16 May, 2020
Reviewers invited
Invitations sent on 15 May, 2020
Editor assigned
On 27 Mar, 2020
Submission checks complete
On 26 Mar, 2020
Editor invited
On 26 Mar, 2020
No comments provided
Editorial decision: Major revision
On 14 Feb, 2020
Review #2 received
Received 29 Jan, 2020
Review #1 received
Received 23 Jan, 2020
Reviewer #2 agreed
On 17 Jan, 2020
Reviewer #1 agreed
On 15 Jan, 2020
Reviewers invited
Invitations sent on 14 Jan, 2020
Editor invited
On 13 Jan, 2020
Editor assigned
On 08 Jan, 2020
First submitted
On 07 Jan, 2020
Submission checks complete
On 07 Jan, 2020
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This preprint is under consideration at BMC Genomic Data. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Fenghua Lan
Xiamen University Medical College
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2812-7145
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 3
Posted 12 Jun, 2020
No comments provided
Editorial decision: Minor revision
On 23 May, 2020
Reviewer #2 agreed
On 18 May, 2020
Review #2 received
Received 18 May, 2020
Reviewer #1 agreed
On 16 May, 2020
Review #1 received
Received 16 May, 2020
Reviewers invited
Invitations sent on 15 May, 2020
Editor assigned
On 27 Mar, 2020
Submission checks complete
On 26 Mar, 2020
Editor invited
On 26 Mar, 2020
No comments provided
Editorial decision: Major revision
On 14 Feb, 2020
Review #2 received
Received 29 Jan, 2020
Review #1 received
Received 23 Jan, 2020
Reviewer #2 agreed
On 17 Jan, 2020
Reviewer #1 agreed
On 15 Jan, 2020
Reviewers invited
Invitations sent on 14 Jan, 2020
Editor invited
On 13 Jan, 2020
Editor assigned
On 08 Jan, 2020
First submitted
On 07 Jan, 2020
Submission checks complete
On 07 Jan, 2020
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Genomic Data.
Background: the disease gene of fragile X syndrome, FMR1 gene, encodes fragile X mental retardation protein (FMRP). The alternative splicing (AS) of FMR1 can affect the structure and function of FMRP. However, the biological functions of alternatively spliced isoforms remain elusive. In a previous study, we identified a new 140 bp exon from the intron 9 of human FMR1 gene. In this study, we further examined the biological functions of this new exon and its underlying signaling pathways.
Results: qRT-PCR results showed that this novel exon is commonly expressed in the peripheral blood of normal individuals. Comparative genomics showed that sequences paralogous to the 140 bp sequence only exist in the genomes of primates. To explore the biological functions of the new transcript, we constructed recombinant eukaryotic expression vectors and lentiviral overexpression vectors. Results showed that the spliced transcript encoded a truncated protein which was expressed mainly in the cell nucleus. Additionally, several genes, including the BEX1 gene involved in mGluR-LTP or mGluR-LTD signaling pathways were significantly influenced when the truncated FMRP was overexpressed.
Conclusions: our work identified a new exon from amid intron 9 of human FMR1 gene with wide expression in normal healthy individuals, which emphasizes the notion that the AS of FMR1 gene is complex and may in a large part account for the multiple functions of FMRP.
Figure 1
Figure 2
Figure 3
Figure 4
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