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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, Vol. 11, No. 24, 3970, 08.12.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Gast, M, Nageswaran, V, Kuss, AW, Tzvetkova, A, Wang, X, Mochmann, LH, Rad, PR, Weiss, S, Simm, S, Zeller, T, Voelzke, H, Hoffmann, W, Völker, U, Felix, SB, Dörr, M, Beling, A, Skurk, C, Leistner, D-M, Rauch, BH, Hirose, T, Heidecker, B, Klingel, K, Nakagawa, S, Poller, WC, Swirski, FK, Haghikia, A & Poller, W 2022, 'tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions', CELLS-BASEL, vol. 11, no. 24, 3970. https://doi.org/10.3390/cells11243970

APA

Gast, M., Nageswaran, V., Kuss, A. W., Tzvetkova, A., Wang, X., Mochmann, L. H., Rad, P. R., Weiss, S., Simm, S., Zeller, T., Voelzke, H., Hoffmann, W., Völker, U., Felix, S. B., Dörr, M., Beling, A., Skurk, C., Leistner, D-M., Rauch, B. H., ... Poller, W. (2022). tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions. CELLS-BASEL, 11(24), [3970]. https://doi.org/10.3390/cells11243970

Vancouver

Gast M, Nageswaran V, Kuss AW, Tzvetkova A, Wang X, Mochmann LH et al. tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions. CELLS-BASEL. 2022 Dec 8;11(24). 3970. https://doi.org/10.3390/cells11243970

Bibtex

@article{f0a4cb06b98a444ba4a0fb4d4fe989aa,
title = "tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions",
abstract = "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.",
keywords = "Humans, Genomics, Immunity, Innate/genetics, Macrophages/immunology, RNA, Long Noncoding/genetics, RNA, Transfer/genetics",
author = "Martina Gast and Vanasa Nageswaran and Kuss, {Andreas W} and Ana Tzvetkova and Xiaomin Wang and Mochmann, {Liliana H} and Rad, {Pegah Ramezani} and Stefan Weiss and Stefan Simm and Tanja Zeller and Henry Voelzke and Wolfgang Hoffmann and Uwe V{\"o}lker and Felix, {Stefan B} and Marcus D{\"o}rr and Antje Beling and Carsten Skurk and David-Manuel Leistner and Rauch, {Bernhard H} and Tetsuro Hirose and Bettina Heidecker and Karin Klingel and Shinichi Nakagawa and Poller, {Wolfram C} and Swirski, {Filip K} and Arash Haghikia and Wolfgang Poller",
year = "2022",
month = dec,
day = "8",
doi = "10.3390/cells11243970",
language = "English",
volume = "11",
journal = "CELLS-BASEL",
issn = "2073-4409",
publisher = "MDPI Multidisciplinary Digital Publishing Institute",
number = "24",

}

RIS

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 -