NDLI: A trans-spliced telomerase RNA dictates telomere synthesis in Trypanosoma brucei

Content Provider	PubMed Central
Author	Sandhu, Ranjodh Sanford, Samantha Basu, Shrabani Park, Mina Pandya, Unnati M. Bibo, Li Chakrabarti, Kausik
Copyright Year	2013
Abstract	Telomerase is a ribonucleoprotein enzyme typically required for sustained cell proliferation. Although both telomerase activity and the telomerase catalytic protein component, TbTERT, have been identified in the eukaryotic pathogen Trypanosoma brucei, the RNA molecule that dictates telomere synthesis remains unknown. Here, we identify the RNA component of Trypanosoma brucei telomerase, TbTR, and provide phylogenetic and in vivo evidence for TbTR's native folding and activity. We show that TbTR is processed through trans-splicing, and is a capped transcript that interacts and copurifies with TbTERT in vivo. Deletion of TbTR caused progressive shortening of telomeres at a rate of 3-5 bp/population doubling (PD), which can be rescued by ectopic expression of a wild-type allele of TbTR in an apparent dose-dependent manner. Remarkably, introduction of mutations in the TbTR template domain resulted in corresponding mutant telomere sequences, demonstrating that telomere synthesis in T. brucei is dependent on TbTR. We also propose a secondary structure model for TbTR based on phylogenetic analysis and chemical probing experiments, thus defining TbTR domains that may have important functional implications in telomere synthesis. Identification and characterization of TbTR not only provide important insights into T. brucei telomere functions, which have been shown to play important roles in T. brucei pathogenesis, but also offer T. brucei as an attractive model system for studying telomerase biology in pathogenic protozoa and for comparative analysis of telomerase function with higher eukaryotes.
Related Links	http://dx.doi.org/10.1038/cr.2013.35
Ending Page	551
Page Count	15
Starting Page	537
File Format	PDF
ISSN	17487838
e-ISSN	17487838
Journal	Cell Research
Issue Number	4
Volume Number	23
Language	English
Publisher	Nature Publishing Group
Publisher Date	2013-04-01
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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A trans-spliced telomerase RNA dictates telomere synthesis in Trypanosoma brucei.

Trypanosoma brucei spliced-leader RNA methylations are required for trans splicing in vivo.

Mapping of branch sites in trans-spliced pre-mRNAs of Trypanosoma brucei.

Proteomic analysis defines the interactome of telomerase in the protozoan parasite, Trypanosoma brucei

Characterization of a Multisubunit Transcription Factor Complex Essential for Spliced-Leader RNA Gene Transcription in Trypanosoma brucei †

The 2′-O-Ribose Methyltransferase for Cap 1 of Spliced Leader RNA and U1 Small Nuclear RNA in Trypanosoma brucei ▿ †

Systematic Study of Sequence Motifs for RNA trans Splicing in Trypanosoma brucei

Consequences of Telomere Shortening at an Active VSG Expression Site in Telomerase-Deficient Trypanosoma brucei ▿ †

Spliced-leader RNA silencing: a novel stress-induced mechanism in Trypanosoma brucei

A trans-spliced telomerase RNA dictates telomere synthesis in Trypanosoma brucei

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A trans-spliced telomerase RNA dictates telomere synthesis in Trypanosoma brucei.

Trypanosoma brucei spliced-leader RNA methylations are required for trans splicing in vivo.

Mapping of branch sites in trans-spliced pre-mRNAs of Trypanosoma brucei.

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Characterization of a Multisubunit Transcription Factor Complex Essential for Spliced-Leader RNA Gene Transcription in Trypanosoma brucei †

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A trans-spliced telomerase RNA dictates telomere synthesis in Trypanosoma brucei