Induction and relocalization of telomeric repeat-containing RNAs during diauxic shift in budding yeast
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Telomeres are maintained in a heterochromatic state that represses transcription of subtelomeric genes, a phenomenon known as telomere position effect. Nevertheless, telomeric DNA is actively transcribed, leading to the synthesis of telomeric repeat-containing noncoding RNA or TERRA. This nuclear noncoding RNA has been proposed to play important roles at telomeres, regulating their silencing, capping, repair and elongation by telomerase. In the budding yeast Saccharomyces cerevisiae, TERRA accumulation is repressed by telomeric silencing and the Rat1 exonuclease. On the other hand, telomere shortening promotes expression of TERRA. So far, little is known about the biological processes that induce TERRA expression in yeast. Understanding the dynamics of TERRA expression and localization is essential to define its function in telomere biology. Here, we aim to study the dynamics of TERRA expression during yeast cell growth. Using live-cell imaging, RNA-FISH and quantitative RT-PCR, we show that TERRA expression is induced as yeast cells undergo diauxic shift, a lag phase during which yeast cells switch their metabolism from anaerobic fermentation to oxidative respiration. This induction is transient as TERRA levels decrease during post-diauxic shift. The increased expression of TERRA is not due to the shortening of telomeres or increased stability of this transcript. Surprisingly, this induction is coincident with a cytoplasmic accumulation of TERRA molecules. Our results suggest that TERRA transcripts may play extranuclear functions with important implications in telomere biology and add a novel layer of complexity in the interplay between telomere biology, metabolism and stress response.
KeywordsTelomeres TERRA Diauxic shift RNA FISH Transcription
This work was supported by a grant from the Canadian Institutes of Health Research (CIHR) MOP-89768. CAPR was supported by a CDMC-CREATE fellowship from the Natural Sciences and Engineering Research Council of Canada (NSERC). ML is supported by a fellowship from the Fonds de Recherche du Québec-Santé (FRQS). PC holds a Research Chair from the FRQS. EC is supported by a Rita Levi-Montalcini fellowship from the Italian Ministry of Education University and Research (MIUR).
- Doksani Y, de Lange T (2014) The role of double-strand break repair pathways at functional and dysfunctional telomeres. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/cshperspect.a016576
- Jain D, Cooper JP (2010) Telomeric strategies: means to an end. Annu Rev Genet 44:243–269. https://doi.org/10.1146/annurev-genet-102108-134841 CrossRefPubMedGoogle Scholar
- Peng B, Williams TC, Henry M, Nielsen LK, Vickers CE (2015) Controlling heterologous gene expression in yeast cell factories on different carbon substrates and across the diauxic shift: a comparison of yeast promoter activities. Microb Cell Fact 14:91. https://doi.org/10.1186/s12934-015-0278-5 CrossRefPubMedPubMedCentralGoogle Scholar
- Tung S-Y, Lee K-W, Hong J-Y, Lee S-P, Shen H-H, Liou G-G (2013) Changes in the genome-wide localization pattern of Sir3 in Saccharomyces cerevisiae during different growth stages. Comput Struct Biotechnol J 7:e201304001. https://doi.org/10.5936/csbj.201304001 CrossRefPubMedPubMedCentralGoogle Scholar