TY - JOUR
T1 - Long non-coding RNA LASSIE regulates shear stress sensing and endothelial barrier function
AU - Stanicek, Laura
AU - Lozano-Vidal, Noelia
AU - Bink, Diewertje Ilse
AU - Hooglugt, Aukie
AU - Yao, Wenjie
AU - Wittig, Ilka
AU - van Rijssel, Jos
AU - van Buul, Jaap Diederik
AU - van Bergen, Anke
AU - Klems, Alina
AU - Ramms, Anne Sophie
AU - Le Noble, Ferdinand
AU - Hofmann, Patrick
AU - Szulcek, Robert
AU - Wang, Sheng Peng
AU - Offermanns, Stefan
AU - Ercanoglu, Meryem Seda
AU - Kwon, Hyouk Bum
AU - Stainier, Didier
AU - Huveneers, Stephan
AU - Kurian, Leo
AU - Dimmeler, Stefanie
AU - Boon, Reinier Abraham
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85085363920&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s42003-020-0987-0
DO - https://doi.org/10.1038/s42003-020-0987-0
M3 - Article
C2 - 32457386
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 265
ER -