LINC00607 facilitates endothelial VEGF-A receptor FLT1 splicing

Area of Science:

• Molecular Biology
• Endothelial Cell Biology
• RNA Biology

Background:

• Aberrant angiogenesis is implicated in preeclampsia.
• Soluble FLT1 (sFLT1), a splice variant of FLT1, acts as a decoy receptor inhibiting VEGF signaling.
• The role of long non-coding RNAs (lncRNAs) in endothelial cell splicing is not well understood.

Purpose of the Study:

• To identify lncRNAs regulating FLT1 alternative splicing.
• To investigate the role of LINC00607 in endothelial biology and vascular diseases.
• To elucidate the mechanism by which LINC00607 controls FLT1 splicing.

Main Methods:

• CRISPR-mediated knockout of LINC00607.
• Assessment of FLT1 splicing and sFLT1 levels.
• RNA-binding assays (LINC00607-U2 snRNA interaction).
• In vitro angiogenesis assays.
• Analysis of LINC00607 and sFLT1 levels in preeclampsia patient samples.

Main Results:

• LINC00607 was identified as a critical regulator of FLT1 alternative splicing.
• Loss of LINC00607 led to increased exon 15 inclusion in FLT1, elevating sFLT1 levels.
• LINC00607 interacts with U2 snRNA, dependent on BRG1, to regulate FLT1 splicing.
• Downregulation of LINC00607 and elevated sFLT1 were observed in preeclampsia.

Conclusions:

• LINC00607 fine-tunes VEGF signaling by regulating FLT1 splicing.
• LINC00607 downregulation contributes to the pathophysiology of preeclampsia.
• Targeting LINC00607-mediated splicing may offer therapeutic potential for vascular diseases.