Long non-coding RNA LASSIE regulates shear stress sensing and endothelial barrier function

Abstract

Blood vessels are constantly exposed to shear stress, a biomechanical force generated by blood flow. Normal shear stress sensing and barrier function are crucial for vascular homeostasis and are controlled by adherens junctions (AJs). Here we show that AJs are stabilized by the shear stress-induced long non-coding RNA LASSIE (linc00520). Silencing of LASSIE in endothelial cells impairs cell survival, cell-cell contacts and cell alignment in the direction of flow. LASSIE associates with junction proteins (e.g. PECAM-1) and the intermediate filament protein nestin, as identified by RNA affinity purification. The AJs component VE-cadherin showed decreased stabilization, due to reduced interaction with nestin and the microtubule cytoskeleton in the absence of LASSIE. This study identifies LASSIE as link between nestin and VE-cadherin, and describes nestin as crucial component in the endothelial response to shear stress. Furthermore, this study indicates that LASSIE regulates barrier function by connecting AJs to the cytoskeleton.

Emerging Roles of Long Noncoding RNAs in the Cytoplasmic Milieu

“…More recently, lncRNA SENCR was suggested to foster ER-localization of the protein CKAP4, which anchors the ER to the cytoskeleton [ 59 ]. Similarly, lncRNA LASSIE colocalizes with ER markers [ 60 ]. While the mechanisms, through which both SENCR and LASSIE control adherence-junction formation in endothelial cells are well-documented (see Section 5 ), their possible roles at the ER demand further investigation.…”

“…Under share-stress conditions, SERCA dislocates CKAP4 away from the plasma membrane, thus promoting formation of adherence-junctions and barrier stabilization [ 59 ]. Another endothelial shear-stress inducible lncRNA is LASSIE, which interacts with adherence-junction protein PECAM-1 and intermediate filament protein Nestin to promote adherence-junction association with the cytoskeleton at the luminal side of the plasma membrane [ 60 ]. Both SENCR and LASSIE were speculated to regulate trafficking of protein complexes between the ER and the plasma membrane [ 59 , 60 ].…”

“…Another endothelial shear-stress inducible lncRNA is LASSIE, which interacts with adherence-junction protein PECAM-1 and intermediate filament protein Nestin to promote adherence-junction association with the cytoskeleton at the luminal side of the plasma membrane [ 60 ]. Both SENCR and LASSIE were speculated to regulate trafficking of protein complexes between the ER and the plasma membrane [ 59 , 60 ]. This aspect, however, requires further investigation.…”

Thinking multi-scale to advance mechanobiology

“…Our Collection published today illustrates how biomechanical factors shape cellular function through influencing the structural integrity, morphology, and dynamics of single cells, ensembles, and tissues. Recent examples are the study by Professor Boon and colleagues identifying a lncRNA involved in shear stress sensing in vasculature 5 and work by Professor Gramolini's lab describing a culture system to study the function of cardiomyocytes 6 . With its broad and interdisciplinary focus, Communications Biology is ideally placed to provide a venue for research at the interface of biology and mechanics.…”

The PNUTS-PP1 axis regulates endothelial aging and barrier function via SEMA3B suppression

“…Endothelial multifrequency resistance was modeled for the calculation of cell-cell adhesion (Rb). Transwell assay was performed as explained elsewhere [32].…”