| Autor: |
Martina Gast, Vanasa Nageswaran, Andreas Kuss, Ana Tzvetkova, Xiaomin Wang, Liliana Mochmann, Pegah Ramezani-Rad, Stefan Weiss, Stefan Simm, Tanja Zeller, Henry Voelzke, Wolfgang Hoffmann, Uwe Völker, Stefan Felix, Marcus Dörr, Antje Beling, Carsten Skurk, David-Manuel Leistner, Bernhard Rauch, Tetsuro Hirose, Bettina Heidecker, Karin Klingel, Shinichi Nakagawa, Wolfram Poller, Filip Swirski, Arash Haghikia, Wolfgang Poller |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-1540419/v2 |
| Popis: |
The evolutionary conserved NEAT1-MALAT1 gene cluster generates large noncoding transcripts remaining nuclear, while tRNA-like transcripts (mascRNA, menRNA) enzymatically generated from these precursors translocate to the cytosol. NEAT1-/- and MALAT1-/- mice display massive atherosclerosis and vascular inflammation. Here, we identify the tRNA-like molecules as critical components of innate immunity. They appear as prototypes of a new class of noncoding RNAs distinct from others (miRNAs, siRNAs) by biosynthetic pathway and intracellular kinetics. CRISPR-generated human ΔmascRNA and ΔmenRNA monocytes/macrophages display defective innate immune sensing, loss of cytokine control, imbalance of growth/angiogenic factor expression impacting upon angiogenesis, and altered cell-cell interaction systems. Antiviral response, foam cell formation/oxLDL uptake, and M1/M2 polarization are defective in ΔmascRNA/ΔmenRNA macrophages, defining the tRNA-like molecules’ first described biological functions. menRNA and mascRNA represent novel components of innate immunity arising from the noncoding genome. Their NEAT1-MALAT1 region of origin appears as archetype of a functionally highly integrated RNA processing system. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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