Proteomics

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A Circular RNA Controls Ribosomal RNA Maturation and Atherosclerosis in Humans


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart, Smooth Muscle Cell

SUBMITTER: Mario Oroshi  

LAB HEAD: Daniel Teupser

PROVIDER: PXD001769 | Pride | 2016-06-10

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20140419_QEp3_PhGe_SA_16.raw Raw
20140419_QEp3_PhGe_SA_17.raw Raw
20140419_QEp3_PhGe_SA_18.raw Raw
20140419_QEp3_PhGe_SA_19.raw Raw
20140419_QEp3_PhGe_SA_20.raw Raw
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