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The long noncoding telomeric repeat containing RNA (TERRA) is expressed at chromosome ends. TERRA upregulation upon experimental manipulation or in ICF (immunodeficiency, centromeric instability, facial anomalies) patients correlates with short telomeres. To study the mechanism of telomere length control by TERRA in Saccharomyces cerevisiae, we mapped the transcriptional start site of TERRA at telomere 1L and inserted a doxycycline regulatable promoter upstream. Induction of TERRA transcription led to telomere shortening of 1L but not of other chromosome ends. TERRA interacts with the Exo1-inhibiting Ku70/80 complex, and deletion of EXO1 but not MRE11 fully suppressed the TERRA-mediated short telomere phenotype in presence and absence of telomerase. Thus TERRA transcription facilitates the 5'-3' nuclease activity of Exo1 at chromosome ends, providing a means to regulate the telomere shortening rate. Thereby, telomere transcription can regulate cellular lifespan through modulation of chromosome end processing activities.
Pubmed ID: 22719262 RIS Download
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The Swiss National Science Foundation (SNSF) is Switzerland''s leading provider of scientific research funding. The SNSF annually supports some 7200 researchers, almost 80 percent of whom are aged 35 years or younger. With its federal mandate, it supports basic research in all disciplines, from philosophy and biology to the nanosciences and medicine. It also invests in applied research in various scientific fields. The focus of its activities is the scientific endorsement of projects submitted by researchers. The best applicants are funded by the SNSF with an annual total amount equalling approximately CHF 700 million. Established in 1952 as a foundation under private law, the SNSF has the autonomy it needs to promote independent scientific research. The SNSF is committed to promoting young scientists and works to ensure that scientific research in Switzerland has the most favourable conditions for developing internationally. It also encourages dialogue between scientists and representatives in society, politics and the economy.
View all literature mentionsA contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)
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