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

Laura Stanicek, Noelia Lozano-Vidal, Diewertje Ilse Bink, Aukie Hooglugt, Wenjie Yao, Ilka Wittig, Jos van Rijssel, Jaap Diederik van Buul, Anke van Bergen, Alina Klems, Anne Sophie Ramms, Ferdinand Le Noble, Patrick Hofmann, Robert Szulcek, Sheng Peng Wang, Stefan Offermanns, Meryem Seda Ercanoglu, Hyouk Bum Kwon, Didier Stainier, Stephan HuveneersLeo Kurian, Stefanie Dimmeler, Reinier Abraham Boon

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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.

Original languageEnglish
Article number265
JournalCommunications Biology
Volume3
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

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