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Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans.
- Source :
-
Nature communications [Nat Commun] 2016 Aug 19; Vol. 7, pp. 12429. Date of Electronic Publication: 2016 Aug 19. - Publication Year :
- 2016
-
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.
- Subjects :
- Apoptosis
Atherosclerosis pathology
Cell Nucleolus metabolism
Cell Proliferation
Chromosomes, Human, Pair 9
Clustered Regularly Interspaced Short Palindromic Repeats
Cyclin-Dependent Kinase Inhibitor p15 genetics
Cyclin-Dependent Kinase Inhibitor p15 metabolism
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p18 genetics
Cyclin-Dependent Kinase Inhibitor p18 metabolism
Gene Expression Profiling
HEK293 Cells
Humans
Macrophages pathology
Muscle, Smooth, Vascular metabolism
Proteins metabolism
RNA Processing, Post-Transcriptional
RNA, Long Noncoding genetics
RNA, Ribosomal genetics
RNA-Binding Proteins
Atherosclerosis genetics
Atherosclerosis metabolism
RNA, Long Noncoding metabolism
RNA, Ribosomal metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 27539542
- Full Text :
- https://doi.org/10.1038/ncomms12429