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

Research output: Contribution to journalJournal articleResearchpeer-review

Lesca M Holdt, Anika Stahringer, Kristina Sass, Garwin Pichler, Nils A Kulak, Wolfgang Wilfert, Alexander Kohlmaier, Andreas Herbst, Bernd H Northoff, Alexandros Nicolaou, Gabor Gäbel, Frank Beutner, Markus Scholz, Joachim Thiery, Kiran Musunuru, Knut Krohn, Matthias Mann, Daniel Teupser

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.

Original languageEnglish
JournalNature Communications
Volume7
Pages (from-to)12429
ISSN2041-1723
DOIs
Publication statusPublished - 19 Aug 2016
Externally publishedYes

    Research areas

  • Journal Article

ID: 184324592