Telomerase Recruitment Requires both TCAB1 and Cajal Bodies Independently

Academic Article

Abstract

  • The ability of most cancer cells to grow indefinitely relies on the enzyme telomerase and its recruitment to telomeres. In human cells, recruitment depends on the Cajal body RNA chaperone TCAB1 binding to the RNA subunit of telomerase (hTR) and is also thought to rely on an N-terminal domain of the catalytic subunit, hTERT. We demonstrate that coilin, an essential structural component of Cajal bodies, is required for endogenous telomerase recruitment to telomeres but that overexpression of telomerase can compensate for Cajal body absence. In contrast, recruitment of telomerase was sensitive to levels of TCAB1, and this was not rescued by overexpression of telomerase. Thus, although Cajal bodies are important for recruitment, TCAB1 has an additional role in this process that is independent of these structures. TCAB1 itself localizes to telomeres in a telomerase-dependent but Cajal body-independent manner. We identify a point mutation in hTERT that largely abolishes recruitment yet does not affect association of telomerase with TCAB1, suggesting that this region mediates recruitment by an independent mechanism. Our results demonstrate that telomerase has multiple independent requirements for recruitment to telomeres and that the function of TCAB1 is to directly transport telomerase to telomeres. © 2012, American Society for Microbiology.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 27398706
  • Author List

  • Stern JL; Zyner KG; Pickett HA; Cohen SB; Bryan TM
  • Start Page

  • 2384
  • End Page

  • 2395
  • Volume

  • 32
  • Issue

  • 13