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

By L. Holdt, Anika Stahringer, Kristina Sass, G. Pichler, N. Kulak, W. Wilfert, Alexander Kohlmaier, A. Herbst, B. Northoff, A. Nicolaou and 8 more. Nature Communications, 2016

978 citations recorded by the source corpus.

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. Circular RNAs are widely expressed in eukaryotic cells but their functions and mechanisms of action are still being elucidated. Here the authors show that circANRILmodulates rRNA maturation and confers protection again atherosclerosis.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c0499eba8917a6493a77971a9be290c80ef00d6b

How researchers see this paper

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In Cancer Research

1. Ling-Ling Chen
2. Li Yang
3. Stas Wüst
4. Sebastian Kadener
5. I. Patop

In Molecular Biology

1. Ling-Ling Chen
2. Li Yang
3. Sebastian Kadener
4. Stas Wüst
5. I. Patop

Citations in the corpus

• Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. (2018, background): “This result suggested that cSMARCA5 may act as a binding platform for AGO2 and miRNAs.”
• Past, present, and future of circRNAs (2019, positive): “Another circRNA, circANRIL , is generally expressed at higher levels than the linear isoform and controls ribosomal RNA (rRNA) maturation by binding to PES1 (pescadillo ribosomal biogenesis factor 1; Holdt et al , 2016).”
• Circular RNA-protein interactions: functions, mechanisms, and identification (2020, background): “circANRIL PES1 impairs pre-rRNA to maturate and ribosome biogenesis in atherosclerosis vascular tissue/smooth muscle cell cytoplasm [47]”
• Circular RNA: metabolism, functions and interactions with proteins (2020, background): “As a result, p53 is activated and accumulates in the nucleus, thus inducing apoptosis in atherosclerotic plaques [114].”
• The Biogenesis, Functions, and Challenges of Circular RNAs. (2018, background): “This circRNA bound to the essential 60S-preribosomal assembly factor pescadillo homolog 1 (PES1) and suppressed ribosome biogenesis in vascular smooth muscle cells and macrophages, resulting in nucleolar stress and cell death, which are key cellular events in atherosclerosis (Burd et al., 2010; Hold”