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
This is a list of supplementary files associated with this preprint. Click to download.
Loading...
Posted 12 Jun, 2020
On 23 May, 2020
On 18 May, 2020
Received 18 May, 2020
On 16 May, 2020
Received 16 May, 2020
Invitations sent on 15 May, 2020
On 27 Mar, 2020
On 26 Mar, 2020
On 26 Mar, 2020
On 14 Feb, 2020
Received 29 Jan, 2020
Received 23 Jan, 2020
On 17 Jan, 2020
On 15 Jan, 2020
Invitations sent on 14 Jan, 2020
On 13 Jan, 2020
On 08 Jan, 2020
On 07 Jan, 2020
On 07 Jan, 2020
Posted 12 Jun, 2020
On 23 May, 2020
On 18 May, 2020
Received 18 May, 2020
On 16 May, 2020
Received 16 May, 2020
Invitations sent on 15 May, 2020
On 27 Mar, 2020
On 26 Mar, 2020
On 26 Mar, 2020
On 14 Feb, 2020
Received 29 Jan, 2020
Received 23 Jan, 2020
On 17 Jan, 2020
On 15 Jan, 2020
Invitations sent on 14 Jan, 2020
On 13 Jan, 2020
On 08 Jan, 2020
On 07 Jan, 2020
On 07 Jan, 2020
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
Loading...