Abstract

Telomerase is a ribonucleoprotein that maintains the ends of linear chromosomes in most eukaryotes. Loss of telomerase activity results in shortening of telomeric DNA and eventually a specific G2/M cell-cycle arrest known as senescence. In humans, telomere shortening occurs during aging, while inappropriate activation of telomerase is associated with approximately 90% of cancers. Previous studies have identified several classes of noncoding RNAs (ncRNA) also associated with aging-related senescence and cancer, but whether ncRNAs are also involved in short-telomere-induced senescence in yeast is unknown. Here, we report 112 putative novel lncRNAs in the yeast Saccharomyces cerevisiae, 41 of which are only expressed in telomerase-negative yeast. Expression of approximately half of the lncRNAs is strongly correlated with that of adjacent genes, suggesting this subset may influence transcription of neighboring genes. Our results reveal a new potential mechanism governing adaptive changes in senescing and post-senescent survivor yeast cells.

Highlights

  • Telomerase is a ribonucleoprotein that maintains the ends of linear chromosomes in most eukaryotes

  • Telomerase establishes telomere length early in lifespan, but the enzyme is aberrantly upregulated in most cancers[1]

  • We identified 112 putative new Long noncoding RNAs (lncRNAs), 41 of which are only upregulated in telomerase-negative cells and that we have termed Telomerase Mutant LncRNAs (TMLs) (Telomerase-Mutant LncRNAs), whereas the remainder represent novel additional SUTs (Stable Unannotated Transcripts)[17]

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Summary

Introduction

Telomerase is a ribonucleoprotein that maintains the ends of linear chromosomes in most eukaryotes. Loss of telomerase activity results in shortening of telomeric DNA and eventually a specific G2/M cell-cycle arrest known as senescence. Telomere shortening occurs during aging, while inappropriate activation of telomerase is associated with approximately 90% of cancers. In the yeast Saccharomyces cerevisiae, cells lacking functional telomerase experience progressive shortening of telomeres and eventually enter a specific cell-cycle arrest in G2/M, known as senescence[4,5,6]. Long noncoding RNAs (lncRNAs) have been implicated in both aging and cancer development[8,9] but a specific link between telomerase and changes in lncRNA expression has not been established. There are additional classes of ncRNAs only expressed under specific circumstances, such as meiosis (MUTs)[15], or in the absence of nonsense-mediated decay (CD-CUTs)[16], underscoring the potential importance of ncRNAs in regulating adaptive changes in S. cerevisiae

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