ABSTRACT
TIN2 is an important regulator of telomere length, and mutations in TINF2, the gene encoding TIN2, cause short-telomere syndromes. While the genetics underscore the importance of TIN2, the mechanism through which TIN2 regulates telomere length remains unclear. Here, we tested the effects of human TIN2 on telomerase activity. We identified a new isoform in human cells, TIN2M, that is expressed at levels similar to those of previously studied TIN2 isoforms. All three TIN2 isoforms localized to and maintained telomere integrity in vivo, and localization was not disrupted by telomere syndrome mutations. Using direct telomerase activity assays, we discovered that TIN2 stimulated telomerase processivity in vitro. All of the TIN2 isoforms stimulated telomerase to similar extents. Mutations in the TPP1 TEL patch abrogated this stimulation, suggesting that TIN2 functions with TPP1/POT1 to stimulate telomerase processivity. We conclude from our data and previously published work that TIN2/TPP1/POT1 is a functional shelterin subcomplex.
FOOTNOTES
- Received 30 December 2018.
- Returned for modification 10 February 2019.
- Accepted 30 July 2019.
- Accepted manuscript posted online 5 August 2019.
Supplemental material for this article may be found at https://doi.org/10.1128/MCB.00593-18.
- Copyright © 2019 Pike et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
