mRNAs encoding telomerase components and regulators are controlled by UPF genes in Saccharomyces cerevisiae.

TitlemRNAs encoding telomerase components and regulators are controlled by UPF genes in Saccharomyces cerevisiae.
Publication TypeJournal Article
Year of Publication2003
AuthorsDahlseid JN, Lew-Smith J, Lelivelt MJ, Enomoto S, Ford A, Desruisseaux M, McClellan M, Lue N, Culbertson MR, Berman J
JournalEukaryot Cell
Volume2
Issue1
Pagination134-42
Date Published2003 Feb
ISSN1535-9778
KeywordsCell Cycle Proteins, Codon, Nonsense, DNA-Binding Proteins, Gene Dosage, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Fungal, Gene Silencing, Genes, Regulator, Mutation, RNA Helicases, RNA, Messenger, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Telomerase, Telomere, Telomere-Binding Proteins
Abstract

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.

DOI10.1128/ec.2.1.134-142.2003
Alternate JournalEukaryot Cell
PubMed ID12582130
PubMed Central IDPMC141172
Grant ListR01 GM065172 / GM / NIGMS NIH HHS / United States
GM38636 / GM / NIGMS NIH HHS / United States
GM65172 / GM / NIGMS NIH HHS / United States

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