tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions
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tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions. / Gast, Martina; Nageswaran, Vanasa; Kuss, Andreas W; Tzvetkova, Ana; Wang, Xiaomin; Mochmann, Liliana H; Rad, Pegah Ramezani; Weiss, Stefan; Simm, Stefan; Zeller, Tanja; Voelzke, Henry; Hoffmann, Wolfgang; Völker, Uwe; Felix, Stefan B; Dörr, Marcus; Beling, Antje; Skurk, Carsten; Leistner, David-Manuel; Rauch, Bernhard H; Hirose, Tetsuro; Heidecker, Bettina; Klingel, Karin; Nakagawa, Shinichi; Poller, Wolfram C; Swirski, Filip K; Haghikia, Arash; Poller, Wolfgang.
in: CELLS-BASEL, Jahrgang 11, Nr. 24, 3970, 08.12.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions
AU - Gast, Martina
AU - Nageswaran, Vanasa
AU - Kuss, Andreas W
AU - Tzvetkova, Ana
AU - Wang, Xiaomin
AU - Mochmann, Liliana H
AU - Rad, Pegah Ramezani
AU - Weiss, Stefan
AU - Simm, Stefan
AU - Zeller, Tanja
AU - Voelzke, Henry
AU - Hoffmann, Wolfgang
AU - Völker, Uwe
AU - Felix, Stefan B
AU - Dörr, Marcus
AU - Beling, Antje
AU - Skurk, Carsten
AU - Leistner, David-Manuel
AU - Rauch, Bernhard H
AU - Hirose, Tetsuro
AU - Heidecker, Bettina
AU - Klingel, Karin
AU - Nakagawa, Shinichi
AU - Poller, Wolfram C
AU - Swirski, Filip K
AU - Haghikia, Arash
AU - Poller, Wolfgang
PY - 2022/12/8
Y1 - 2022/12/8
N2 - 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. Whereas functions have been assigned to the nuclear transcripts, data on biological functions of the small cytosolic transcripts are sparse. We previously found NEAT1-/- and MALAT1-/- mice to display massive atherosclerosis and vascular inflammation. Here, employing selective targeted disruption of menRNA or mascRNA, we investigate the tRNA-like molecules as critical components of innate immunity. 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 first biological functions of menRNA and describing new functions of mascRNA. menRNA and mascRNA represent novel components of innate immunity arising from the noncoding genome. They appear as prototypes of a new class of noncoding RNAs distinct from others (miRNAs, siRNAs) by biosynthetic pathway and intracellular kinetics. Their NEAT1-MALAT1 region of origin appears as archetype of a functionally highly integrated RNA processing system.
AB - 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. Whereas functions have been assigned to the nuclear transcripts, data on biological functions of the small cytosolic transcripts are sparse. We previously found NEAT1-/- and MALAT1-/- mice to display massive atherosclerosis and vascular inflammation. Here, employing selective targeted disruption of menRNA or mascRNA, we investigate the tRNA-like molecules as critical components of innate immunity. 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 first biological functions of menRNA and describing new functions of mascRNA. menRNA and mascRNA represent novel components of innate immunity arising from the noncoding genome. They appear as prototypes of a new class of noncoding RNAs distinct from others (miRNAs, siRNAs) by biosynthetic pathway and intracellular kinetics. Their NEAT1-MALAT1 region of origin appears as archetype of a functionally highly integrated RNA processing system.
KW - Humans
KW - Genomics
KW - Immunity, Innate/genetics
KW - Macrophages/immunology
KW - RNA, Long Noncoding/genetics
KW - RNA, Transfer/genetics
U2 - 10.3390/cells11243970
DO - 10.3390/cells11243970
M3 - SCORING: Journal article
C2 - 36552736
VL - 11
JO - CELLS-BASEL
JF - CELLS-BASEL
SN - 2073-4409
IS - 24
M1 - 3970
ER -