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Science. 2015 Sep 18;349(6254):1356-8. doi: 10.1126/science.aac5677.

Pri sORF peptides induce selective proteasome-mediated protein processing.

Author information

1
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.
2
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
3
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.
4
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.

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.

PMID:
26383956
DOI:
10.1126/science.aac5677
[Indexed for MEDLINE]
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