Evidence map›Paper›PMID 29804836›Full record

ArticleCell2018

An Activity Switch in Human Telomerase Based on RNA Conformation and Shaped by TCAB1.

Lu Chen, Caitlin M Roake, Adam Freund, Pedro J Batista, Siqi Tian, Yi A Yin, Chandresh R Gajera, Shengda Lin, Byron Lee, Matthew F Pech and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 86 citations in OpenAlex.

  1. Review
  2. Article
  3. Biogenesis and Regulation of Telomerase during Development and Cancer.Cold Spring Harbor perspectives in biology · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Advances in understanding telomerase assembly.Biochemical Society transactions · 2023
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Lu ChenDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Caitlin M RoakeDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Adam FreundDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Pedro J BatistaCenter for Personal Dynamic Regulomes and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Siqi TianDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Yi A YinDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Chandresh R GajeraDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Shengda LinDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Byron LeeCenter for Personal Dynamic Regulomes and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Matthew F PechDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Andrew S VenteicherDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Rhiju DasDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Howard Y ChangCenter for Personal Dynamic Regulomes and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Steven E ArtandiDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: sartandi@stanford.edu.
Stanford University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
Next-generation computational/chemical methods for complex RNA structuresR35GM122579 · NIGMS · STANFORD UNIVERSITY · PI Rhiju Das · 2017 to 2026
$7.2M
REVERSING CELLULAR IMMORTALITY IN CANCERR35CA197563 · NCI · STANFORD UNIVERSITY · PI ARTANDI, STEVEN E · 2015 to 2021
$6.4M
Structural Motifs in RNAR01HG004361 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2007 to 2018
$4.7M
Determining the role of TCAB1 in shaping telomerase functionR01AG056575 · NIA · STANFORD UNIVERSITY · PI ARTANDI, STEVEN E · 2017 to 2021
$2.3M
Non-coding RNA Structure through a Mutate-and-Map StrategyR01GM102519 · NIGMS · STANFORD UNIVERSITY · PI DAS, RHIJU · 2012 to 2016
$1.5M
NCI NIH HHS R35 CA197563NHGRI NIH HHS R01 HG004361NIA NIH HHS R01 AG056575NIGMS NIH HHS R01 GM102519NIGMS NIH HHS R35 GM122579NIGMS NIH HHS T32 GM007365
6 · The paper itself

Abstract

Ribonucleoprotein enzymes require dynamic conformations of their RNA constituents for regulated catalysis. Human telomerase employs a non-coding RNA (hTR) with a bipartite arrangement of domains-a template-containing core and a distal three-way junction (CR4/5) that stimulates catalysis through unknown means. Here, we show that telomerase activity unexpectedly depends upon the holoenzyme protein TCAB1, which in turn controls conformation of CR4/5. Cells lacking TCAB1 exhibit a marked reduction in telomerase catalysis without affecting enzyme assembly. Instead, TCAB1 inactivation causes unfolding of CR4/5 helices that are required for catalysis and for association with the telomerase reverse-transcriptase (TERT). CR4/5 mutations derived from patients with telomere biology disorders provoke defects in catalysis and TERT binding similar to TCAB1 inactivation. These findings reveal a conformational "activity switch" in human telomerase RNA controlling catalysis and TERT engagement. The identification of two discrete catalytic states for telomerase suggests an intramolecular means for controlling telomerase in cancers and progenitor cells.

Indexed as

BiocatalysisCell LineHeLa CellsHumansMolecular ChaperonesNuclear ProteinsNucleic Acid ConformationProtein BindingRNA InterferenceRNA, Small InterferingRNA, UntranslatedTelomeraseTelomereMolecular ChaperonesNuclear Proteinsp80-coilinRNA, Small InterferingRNA, UntranslatedTelomeraseTERT protein, humanWRAP53 protein, humanCAB boxCajal bodyCR4/5dyskeratosis congenitalH/ACA RNPicSHAPERNA foldingTCAB1telomerasetelomere

Identifiers

PMID29804836
PMCPMC6063371
OpenAlexW2803766971

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.