SENCR stabilizes vascular endothelial cell adherens junctions through interaction with CKAP4

Area of Science:

• Molecular Biology
• Vascular Biology
• Genomics

Background:

• SENCR is a human-specific long noncoding RNA (lncRNA) found in vascular cells.
• Its precise function and regulatory mechanisms in endothelial cells (ECs) remain largely unknown.

Purpose of the Study:

• To elucidate the role and mechanism of SENCR in regulating endothelial cell phenotypes, particularly in response to shear stress.
• To identify SENCR-interacting proteins and understand their functional consequences.

Main Methods:

• Analysis of SENCR RNA levels in human ECs under laminar shear stress.
• In vivo studies using humanized SENCR-expressing mice subjected to varying shear stress.
• SENCR loss-of-function experiments.
• Biotinylated RNA pull-down assays coupled with mass spectrometry.
• RNA immunoprecipitation (RIP) and co-immunoprecipitation (Co-IP).

Main Results:

• SENCR RNA levels increase in ECs under laminar shear stress and in specific aortic regions of mice.
• SENCR depletion causes EC membrane instability and increased permeability.
• CKAP4 is identified as a key SENCR-binding protein.
• SENCR knockdown leads to increased cell surface CKAP4 and enhanced CKAP4-CDH5 interaction, destabilizing adherens junctions.

Conclusions:

• SENCR is a flow-responsive lncRNA crucial for maintaining endothelial cell adherens junction integrity.
• SENCR promotes EC barrier function by interacting with CKAP4, which stabilizes cell membrane-bound CDH5.