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

TY - JOUR

T1 - Telomerase RNA stem terminus element affects template boundary element function, telomere sequence, and shelterin binding

AU - Webb, Christopher J.

AU - Zakian, Virginia A.

PY - 2015/9/8

Y1 - 2015/9/8

N2 - 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 sequencewas 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 fromthe template, ensures proper telomere sequence, which in turn promotes proper assembly of the shelterin complex.

AB - 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 sequencewas 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 fromthe template, ensures proper telomere sequence, which in turn promotes proper assembly of the shelterin complex.

KW - Pot1

KW - Stem terminus element

KW - Taz1

KW - Telomerase RNA

KW - Telomere repeat

UR - https://www.scopus.com/pages/publications/84941249191

UR - https://www.scopus.com/pages/publications/84941249191#tab=citedBy

U2 - 10.1073/pnas.1503157112

DO - 10.1073/pnas.1503157112

M3 - Article

C2 - 26305931

SN - 0027-8424

VL - 112

SP - 11312

EP - 11317

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 36

ER -