Analyses of the Life Cycle of TLC1 and the Nuclear RNA Quality Control System in Saccharomyces cerevisiae
by Haijia Wu
Date of Examination:2015-04-23
Date of issue:2015-04-24
Advisor:Prof. Dr. Heike Krebber
Referee:Prof. Dr. Heike Krebber
Referee:PD Dr. Wilfried Kramer
Referee:Prof. Dr. Gerhard Braus
Referee:Prof. Dr. Ralf Ficner
Referee:Prof. Dr. Stefanie Pöggeler
Referee:Prof. Dr. Kai Heimel
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Abstract
English
During genome replication, chromosomes undergo a progressive shortening of their ends. To counteract this loss, a complex named telomerase functions as a reverse transcriptase to elongate telomeres. In Saccharomyces cerevisiae, telomerase contains a non-coding RNA, TLC1, which serves as a scaffold for formation of the telomerase complex and the template for the reverse transcription to elongate the telomeres. Upon its synthesis, TLC1 undergoes a series of nuclear and cytoplasmic maturation steps. Here it has been shown that the TLC1 nuclear export is dependent on the classic mRNA export pathway in addition to the already known Crm1/Xpo1 pathway. The nuclear export defects that occur upon mutation of these pathways impair the formation of the telomerase, as well as its final localisation suggesting an essential role of TLC1 shuttling in telomerase assembly. Consequently, the TLC1 nuclear transport defect leads to telomeric shortening indicating a necessity of the TLC1 shuttling for telomere maintenance. Moreover, the nuclear RNA quality control system, composed of the TRAMP complex and nuclear exosome, might mediate the nuclear maturation of TLC1. Finally, it has also been pointed out that the localisation and maturation of the nuclear quality control system might be regulated by a nuclear importer, Mtr10, which is also involved in TLC1 nuclear import.
Keywords: TLC1; non-coding RNA; Telomerase; nuclear transport; Mex67; Xpo1