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  Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans

Holdt, L. M., Stahringer, A., Sass, K., Pichler, G., Kulak, N. A., Wilfert, W., et al. (2016). Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nature Communications, 7: 12429. doi:10.1038/ncomms12429.

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 Creators:
Holdt, Lesca M.1, Author
Stahringer, Anika1, Author
Sass, Kristina1, Author
Pichler, Garwin2, Author              
Kulak, Nils A.2, Author              
Wilfert, Wolfgang1, Author
Kohlmaier, Alexander1, Author
Herbst, Andreas1, Author
Northoff, Bernd H.1, Author
Nicolaou, Alexandros1, Author
Gaebel, Gabor1, Author
Beutner, Frank1, Author
Scholz, Markus1, Author
Thiery, Joachim1, Author
Musunuru, Kiran1, Author
Krohn, Knut1, Author
Mann, Matthias2, Author              
Teupser, Daniel1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: CORONARY-ARTERY-DISEASE; CELL-PROLIFERATION; ASSOCIATION ANALYSIS; BINDING PROTEINS; CHROMOSOME 9P21; SRY TRANSCRIPT; MOUSE TESTIS; IN-VIVO; BIOGENESIS; P53Science & Technology - Other Topics;
 Abstract: Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their molecular mechanism in human disease remains obscure. Here we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers atheroprotection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. CircANRIL binds to pescadillo homologue 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis in vascular smooth muscle cells and macrophages. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key cell functions in atherosclerosis. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring atheroprotection, thereby showing that circularization of long non-coding RNAs may alter RNA function and protect from human disease.

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Language(s): eng - English
 Dates: 2015-10-152016-07-012016-08-19
 Publication Status: Published online
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000381773000001
DOI: 10.1038/ncomms12429
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 7 Sequence Number: 12429 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723