RNase III-dependent regulation of yeast telomerase.
In bakers' yeast, in vivo telomerase activity requires a ribonucleoprotein (RNP) complex with at least four associated proteins (Est2p, Est1p, Est3p, and Cdc13p) and one RNA species (Tlc1). The function of telomerase in maintaining chromosome ends, called telomeres, is tightly regulated and linked to the cell cycle. However, the mechanisms that regulate the expression of individual components of telomerase are poorly understood. Here we report that yeast RNase III (Rnt1p), a double-stranded RNA-specific endoribonuclease, regulates the expression of telomerase subunits and is required for maintaining normal telomere length. Deletion or inactivation of RNT1 induced the expression of Est1, Est2, Est3, and Tlc1 RNAs and increased telomerase activity, leading to elongation of telomeric repeat tracts. In silico analysis of the different RNAs coding for the telomerase subunits revealed a canonical Rnt1p cleavage site near the 3' end of Est1 mRNA. This predicted structure was cleaved by Rnt1p and its disruption abolished cleavage in vitro. Mutation of the Rnt1p cleavage signal in vivo impaired the cell cycle-dependent degradation of Est1 mRNA without affecting its steady-state level. These results reveal a new mechanism that influences telomeres length by controlling the expression of the telomerase subunits.
Larose
Stéphanie
S
RNA Group, Département de Microbiologie et d'Infectiologie, Facultéde Médecine, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
Laterreur
Nancy
N
RNA Group, Département de Microbiologie et d'Infectiologie, Facultéde Médecine, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
Ghazal
Ghada
G
RNA Group, Département de Microbiologie et d'Infectiologie, Facultéde Médecine, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
Gagnon
Jules
J
RNA Group, Département de Microbiologie et d'Infectiologie, Facultéde Médecine, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
Wellinger
Raymund J
RJ
RNA Group, Département de Microbiologie et d'Infectiologie, Facultéde Médecine, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
Elela
Sherif Abou
SA
RNA Group, Département de Microbiologie et d'Infectiologie, Facultéde Médecine, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada. Electronic address: sherif.abou.elela@usherbrooke.ca.
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D016615:Telomere / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D021122:Protein Subunits; D012331:RNA, Fungal; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; C099024:EST1 protein, S cerevisiae; D019098:Telomerase; C468367:RNT1 protein, S cerevisiae; D043244:Ribonuclease III