Circular L-RNA aptamer promotes target recognition and controls gene activity.
Ontology highlight
ABSTRACT:
SUBMITTER: Ji D
PROVIDER: S-EPMC8287958 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their role in human health and 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 athero-protection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. At the molecular level, circANRIL competes with precursor rRNA (pre-rRNA) for binding to pescadillo homolog 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key athero-protective cell functions within the arterial wall. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring athero-protection, thereby unveiling a therapeutic potential of certain circRNAs in human disease.
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