The telomerase inhibitor Gno1p/PINX1 activates the helicase Prp43p during ribosome biogenesis.
We provide evidence that a central player in ribosome synthesis, the ribonucleic acid helicase Prp43p, can be activated by yeast Gno1p and its human ortholog, the telomerase inhibitor PINX1. Gno1p and PINX1 expressed in yeast interact with Prp43p and the integrity of their G-patch domain is required for this interaction. Moreover, PINX1 interacts with human PRP43 (DHX15) in HeLa cells. PINX1 directly binds to yeast Prp43p and stimulates its adenosine triphosphatase activity, while alterations of the G patch abolish formation of the PINX1/Prp43p complex and the stimulation of Prp43p. In yeast, lack of Gno1p leads to a decrease in the levels of pre-40S and intermediate pre-60S pre-ribosomal particles, defects that can be corrected by PINX1 expression. We show that Gno1p associates with 90S and early pre-60S pre-ribosomal particles and is released from intermediate pre-60S particles. G-patch alterations in Gno1p or PINX1 that inhibit their interactions with Prp43p completely abolish their function in yeast ribosome biogenesis. Altogether, our results suggest that activation of Prp43p by Gno1p/PINX1 within early pre-ribosomal particles is crucial for their subsequent maturation.
Equipe labellisée Ligue Contre le Cancer, LBME, CNRS and Toulouse University, Toulouse 31062, France.
Yan-Ling
YL
Chen
Equipe labellisée Ligue Contre le Cancer, LBME, CNRS and Toulouse University, Toulouse 31062, France.
Régine
R
Capeyrou
Equipe labellisée Ligue Contre le Cancer, LBME, CNRS and Toulouse University, Toulouse 31062, France.
Odile
O
Humbert
Equipe labellisée Ligue Contre le Cancer, LBME, CNRS and Toulouse University, Toulouse 31062, France.
Saïda
S
Mouffok
Equipe labellisée Ligue Contre le Cancer, LBME, CNRS and Toulouse University, Toulouse 31062, France.
Yasmine Al
YA
Kadri
Equipe labellisée Ligue Contre le Cancer, LBME, CNRS and Toulouse University, Toulouse 31062, France.
Simon
S
Lebaron
Equipe labellisée Ligue Contre le Cancer, LBME, CNRS and Toulouse University, Toulouse 31062, France henras@ibcg.biotoul.fr.
Anthony K
AK
Henras
Equipe labellisée Ligue Contre le Cancer, LBME, CNRS and Toulouse University, Toulouse 31062, France henry@ibcg.biotoul.fr.
Yves
Y
Henry
D000251:Adenosine Triphosphatases / Q000378:metabolism; D018797:Cell Cycle Proteins; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D019098:Telomerase / Q000037:antagonists & inhibitors; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
D018797:Cell Cycle Proteins; C000590779:Gno1 protein, S cerevisiae; C440808:PINX1 protein, human; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; C539469:DHX15 protein, human; D019098:Telomerase; D000251:Adenosine Triphosphatases; C109034:PRP43 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases