title: Pri sORF peptides induce selective proteasome-mediated protein processing.
abstract: A wide variety of RNAs encode small open-reading-frame (smORF/sORF) peptides, but their functions are largely unknown. Here, we show that Drosophila polished-rice (pri) sORF peptides trigger proteasome-mediated protein processing, converting the Shavenbaby (Svb) transcription repressor into a shorter activator. A genome-wide RNA interference screen identifies an E2-E3 ubiquitin-conjugating complex, UbcD6-Ubr3, which targets Svb to the proteasome in a pri-dependent manner. Upon interaction with Ubr3, Pri peptides promote the binding of Ubr3 to Svb. Ubr3 can then ubiquitinate the Svb N terminus, which is degraded by the proteasome. The C-terminal domains protect Svb from complete degradation and ensure appropriate processing. Our data show that Pri peptides control selectivity of Ubr3 binding, which suggests that the family of sORF peptides may contain an extended repertoire of protein regulators.
authors.affiliation: Centre de Biologie du Développement, Université de Toulouse III-Paul Sabatier, Bâtiment 4R3, 118 route de Narbonne, F-31062 Toulouse, France. CNRS, UMR5547, Centre de Biologie du Développement, F-31062 Toulouse, France.
authors.forename: J
authors.initials: J
authors.lastname: Zanet
authors.affiliation: Centre de Biologie du Développement, Université de Toulouse III-Paul Sabatier, Bâtiment 4R3, 118 route de Narbonne, F-31062 Toulouse, France. CNRS, UMR5547, Centre de Biologie du Développement, F-31062 Toulouse, France.
authors.forename: E
authors.initials: E
authors.lastname: Benrabah
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.affiliation: Centre de Biologie du Développement, Université de Toulouse III-Paul Sabatier, Bâtiment 4R3, 118 route de Narbonne, F-31062 Toulouse, France. CNRS, UMR5547, Centre de Biologie du Développement, F-31062 Toulouse, France.
authors.forename: A
authors.initials: A
authors.lastname: Pélissier-Monier
authors.affiliation: Centre de Biologie du Développement, Université de Toulouse III-Paul Sabatier, Bâtiment 4R3, 118 route de Narbonne, F-31062 Toulouse, France. CNRS, UMR5547, Centre de Biologie du Développement, F-31062 Toulouse, France.
authors.forename: H
authors.initials: H
authors.lastname: Chanut-Delalande
authors.affiliation: Centre de Biologie du Développement, Université de Toulouse III-Paul Sabatier, Bâtiment 4R3, 118 route de Narbonne, F-31062 Toulouse, France. CNRS, UMR5547, Centre de Biologie du Développement, F-31062 Toulouse, France.
authors.forename: B
authors.initials: B
authors.lastname: Ronsin
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA. Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Neurological Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Bellen
authors.affiliation: Centre de Biologie du Développement, Université de Toulouse III-Paul Sabatier, Bâtiment 4R3, 118 route de Narbonne, F-31062 Toulouse, France. CNRS, UMR5547, Centre de Biologie du Développement, F-31062 Toulouse, France. francois.payre@univ-tlse3.fr serge.plaza@univ-tlse3.f.
authors.forename: F
authors.initials: F
authors.lastname: Payre
authors.affiliation: Centre de Biologie du Développement, Université de Toulouse III-Paul Sabatier, Bâtiment 4R3, 118 route de Narbonne, F-31062 Toulouse, France. CNRS, UMR5547, Centre de Biologie du Développement, F-31062 Toulouse, France. francois.payre@univ-tlse3.fr serge.plaza@univ-tlse3.f.
authors.forename: S
authors.initials: S
authors.lastname: Plaza
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D034622:RNA Interference; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D010455:Peptides; D014157:Transcription Factors; C089512:ovo protein, Drosophila; C489286:Ubc6 protein, Drosophila; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C000599363:Ubr3 protein, Drosophila