Telomerase RNA stem terminus element affects template boundary element function, telomere sequence, and shelterin binding.

TitleTelomerase RNA stem terminus element affects template boundary element function, telomere sequence, and shelterin binding.
Publication TypeJournal Article
Year of Publication2015
AuthorsWebb, CJ, Zakian, VA
JournalProc Natl Acad Sci U S A
Volume112
Issue36
Pagination11312-7
Date Published2015 Sep 08
ISSN1091-6490
KeywordsAutophagy-Related Proteins, Base Sequence, Blotting, Western, Chromosomal Proteins, Non-Histone, In Situ Hybridization, Fluorescence, Insulator Elements, Models, Genetic, Mutation, Protein Binding, Regulatory Sequences, Ribonucleic Acid, Reverse Transcriptase Polymerase Chain Reaction, Reverse Transcription, RNA, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sequence Homology, Nucleic Acid, Telomerase, Telomere, Telomere-Binding Proteins, Templates, Genetic, Transcription Factors
Abstract

<p>The stem terminus element (STE), which was discovered 13 y ago in human telomerase RNA, is required for telomerase activity, yet its mode of action is unknown. We report that the Schizosaccharomyces pombe telomerase RNA, TER1 (telomerase RNA 1), also contains a STE, which is essential for telomere maintenance. Cells expressing a partial loss-of-function TER1 STE allele maintained short stable telomeres by a recombination-independent mechanism. Remarkably, the mutant telomere sequence was different from that of wild-type cells. Generation of the altered sequence is explained by reverse transcription into the template boundary element, demonstrating that the STE helps maintain template boundary element function. The altered telomeres bound less Pot1 (protection of telomeres 1) and Taz1 (telomere-associated in Schizosaccharomyces pombe 1) in vivo. Thus, the S. pombe STE, although distant from the template, ensures proper telomere sequence, which in turn promotes proper assembly of the shelterin complex. </p>

DOI10.1073/pnas.1503157112
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID26305931
PubMed Central IDPMC4568702
Grant ListR01 GM043265 / GM / NIGMS NIH HHS / United States
R35 GM118279 / GM / NIGMS NIH HHS / United States
R37 GM026938 / GM / NIGMS NIH HHS / United States
GM043265 / GM / NIGMS NIH HHS / United States