A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation.
2017
Conn, Vanessa, M. | Hugouvieux, Véronique | Nayak, Aditya | Conos, Stephanie A | Capovilla, Giovanna | Cildir, Gökhan | Jourdain, Agnès | Tergaonkar, Vinay | Schmid, Markus | Zubieta, Chloe | Conn, Simon, J. | Centre for Cancer Biology ; Hanson Institute, Adelaide | Physiologie cellulaire et végétale (LPCV) ; Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG) ; Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA) | Department of Molecular Biology [Tübingen] ; Max Planck Institute for Developmental Biology ; Max-Planck-Gesellschaft-Max-Planck-Gesellschaft | Department of Biochemistry, Yong Loo Lin School of Medicine and Department of Biological Sciences ; National University of Singapore (NUS) | Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology | Umeå Plant Science Centre, Department of Plant Physiology ; Umeå University = Umeå Universitet | ANR (FLOPINET) ; CNRS ; NHMRC [GNT1089167] ; Australian Research Council [FT160100318] ; ATIP-Avenir ; LabEx GRAL [ANR-10-LABX-49-01] ; South Australian Government Department of State Development ; CEA Irtelis fellowship | ANR-16-CE92-0023,FLOPINET,Floral Pioneer Factors(2016) | ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010)
Simon J. Conn ([email protected])
Show more [+] Less [-]International audience
Show more [+] Less [-]English. 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.
Show more [+] Less [-]AGROVOC Keywords
Bibliographic information
This bibliographic record has been provided by Institut national de la recherche agronomique