Lab. IMoPA UMR 7365 CNRS/UL - UNIVERSITÉ DE LORRAINE « Synergistic defects in pre-rRNA processing from mutations in the U3-specific protein Rrp9 and U3 snoRNA. »
Nucleic Acids Res. 2020 Apr 17;48(7):3848-3868. Clerget G, Bourguignon-Igel V, Marmier-Gourrier N, Rolland N, Wacheul L, Manival X, Charron C, Kufel J, Méreau A, Senty-Ségault V, Tollervey D, Lafontaine DLJ, Branlant C, Rederstorff M.
http://doi.org/10.1093/nar/gkaa066
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Guillaume Clerget is 33 years old and teaches now Biochemistry, Molecular Biology, Pharmacology and Histology to students attending medical studies at the Lorraine University in Nancy. He obtained a Master's degree in « Biochemistry, Molecular and Cellular Biology» at the Lorraine University. During his PhD, carried out in Team 1 of the IMoPA laboratory, headed by Bruno Charpentier and Yuri Motorin, he was mainly interested in pre-rRNA processing in the yeast S. cerevisiae and more precisely in the study of the U3 snoRNP and its specific protein Rrp9. In the selected publication, Guillaume Clerget and co-workers have identified a crucial amino acid at the surface of the Rrp9 β-propeller, a novel protein–protein interaction network and roles for key segments of the U3 5’-terminal region. Based on these results, a new model for U3 binding to the yeast pre-rRNA is proposed.
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Laboratoire IMoPA UMR 7365 CNRS/UL
Equipe ARN, RNP - Maturation, Structure, Fonction -
Université de Lorraine
Biopôle/Campus Médecine Brabois
9 Avenue de la Forêt de Haye
BP20199
54505 Vandoeuvre-lès-Nancy
FRANCE
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Résumé de l'article
U3 snoRNA and the associated Rrp9/U3-55K protein are essential for 18S rRNA production by the SSU-processome complex. U3 and Rrp9 are required for early pre-rRNA cleavages at sites A0, A1 and A2, but the mechanism remains unclear. Substitution of Arg 289 in Rrp9 to Ala (R289A) specifically reduced cleavage at sites A1 and A2. Surprisingly, R289 is located on the surface of the Rrp9 β-propeller structure opposite to U3 snoRNA. To understand this, we first characterized the protein-protein interaction network of Rrp9 within the SSU-processome. This identified a direct interaction between the Rrp9 β-propeller domain and Rrp36, the strength of which was reduced by the R289A substitution, implicating this interaction in the observed processing phenotype. The Rrp9 R289A mutation also showed strong synergistic negative interactions with mutations in U3 that destabilize the U3/pre-rRNA base-pair interactions or reduce the length of their linking segments. We propose that the Rrp9 β-propeller and U3/pre-rRNA binding cooperate in the structure or stability of the SSU-processome. Additionally, our analysis of U3 variants gave insights into the function of individual segments of the 5 -terminal 72nt sequence of U3. We interpret these data in the light of recently reported SSU-processome structures.
