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Article Dans Une Revue Nature Plants Année : 2017

A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation.

Résumé

Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing. These single-stranded, covalently-closed circRNA molecules have been identified in all eukaryotic kingdoms of life(1), yet their functions have remained elusive. Here, we report that circRNAs can be used as $bona\ fide$ biomarkers of functional, exon-skipped AS variants in $Arabidopsis$, including in the homeotic MADS-box transcription factor family. Furthermore, we demonstrate that circRNAs derived from exon 6 of the SEPALLATA3 (SEP3) gene increase abundance of the cognate exon-skipped AS variant (SEP3.3 which lacks exon 6), in turn driving floral homeotic phenotypes. Toward demonstrating the underlying mechanism, we show that the SEP3 exon 6 circRNA can bind strongly to its cognate DNA locus, forming an RNA:DNA hybrid, or R-loop, whereas the linear RNA equivalent bound significantly more weakly to DNA. R-loop formation results in transcriptional pausing, which has been shown to coincide with splicing factor recruitment and AS(2-4). This report presents a novel mechanistic insight for how at least a subset of circRNAs probably contribute to increased splicing efficiency of their cognate exon-skipped messenger RNA and provides the first evidence of an organismal-level phenotype mediated by circRNA manipulation.
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Dates et versions

hal-01518285 , version 1 (04-05-2017)

Identifiants

Citer

Vanessa M. Conn, Véronique Hugouvieux, Aditya Nayak, Stephanie A Conos, Giovanna Capovilla, et al.. A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation.. Nature Plants, 2017, 3 (5), pp.17053. ⟨10.1038/nplants.2017.53⟩. ⟨hal-01518285⟩
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