mRNAs encoding telomerase components and regulators are controlled by UPF genes in Saccharomyces cerevisiae.
Telomeres, the chromosome ends, are maintained by a balance of activities that erode and replace the terminal DNA sequences. Furthermore, telomere-proximal genes are often silenced in an epigenetic manner. In Saccharomyces cerevisiae, average telomere length and telomeric silencing are reduced by loss of function of UPF genes required in the nonsense-mediated mRNA decay (NMD) pathway. Because NMD controls the mRNA levels of several hundred wild-type genes, we tested the hypothesis that NMD affects the expression of genes important for telomere functions. In upf mutants, high-density oligonucleotide microarrays and Northern blots revealed that the levels of mRNAs were increased for genes encoding the telomerase catalytic subunit (Est2p), in vivo regulators of telomerase (Est1p, Est3p, Stn1p, and Ten1p), and proteins that affect telomeric chromatin structure (Sas2p and Orc5p). We investigated whether overexpressing these genes could mimic the telomere length and telomeric silencing phenotypes seen previously in upf mutant strains. Increased dosage of STN1, especially in combination with increased dosage of TEN1, resulted in reduced telomere length that was indistinguishable from that in upf mutants. Increased levels of STN1 together with EST2 resulted in reduced telomeric silencing like that of upf mutants. The half-life of STN1 mRNA was not altered in upf mutant strains, suggesting that an NMD-controlled transcription factor regulates the levels of STN1 mRNA. Together, these results suggest that NMD maintains the balance of gene products that control telomere length and telomeric silencing primarily by maintaining appropriate levels of STN1, TEN1, and EST2 mRNA.
Dahlseid
Jeffrey N
JN
Department of Chemistry, St Olaf College, Northfield, Minnesota 55057, USA.
Lew-Smith
Jodi
J
Lelivelt
Michael J
MJ
Enomoto
Shinichiro
S
Ford
Amanda
A
Desruisseaux
Michelle
M
McClellan
Mark
M
Lue
Neal
N
Culbertson
Michael R
MR
Berman
Judith
J
D018797:Cell Cycle Proteins / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics*; D004268:DNA-Binding Proteins; D018628:Gene Dosage; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D020868:Gene Silencing / Q000502:physiology; D005809:Genes, Regulator / Q000235:genetics; D009154:Mutation / Q000235:genetics; D020365:RNA Helicases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics
D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C428109:Stn1 protein, S cerevisiae; D034501:Telomere-Binding Proteins; C509185:EST2 protein, S cerevisiae; D019098:Telomerase; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases