A structurally conserved human and Tetrahymena telomerase catalytic core

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Telomerase is essential for maintaining chromosome ends, preventing cellular aging.
• The catalytic core of telomerase comprises telomerase reverse transcriptase (TERT) and telomerase RNA (TER).
• The precise structural definition and evolutionary conservation of TERT domains remain incompletely understood.

Purpose of the Study:

• To investigate the evolutionary conservation of TERT domains, specifically TRAP and TEN.
• To build a more complete pseudoatomic model of the human telomerase catalytic core.
• To elucidate the conserved interactions between TERT and TER domains regulating telomere synthesis.

Main Methods:

• Multiple sequence alignments and statistical coupling analysis of identified TERT proteins.
• Integration of bioinformatic data with cryoelectron microscopy structures of Tetrahymena telomerase.
• Construction of a pseudoatomic model of the human telomerase catalytic core.

Main Results:

• Identified TRAP and TEN as telomerase-specific domains that have coevolved.
• Demonstrated the presence and conserved interactions of TEN and TRAP across species.
• Developed a comprehensive pseudoatomic model of the human telomerase catalytic core, incorporating TER and TERT domains.

Conclusions:

• The TEN-TRAP complex is a conserved feature of TERT, critical for telomerase activity.
• The new model provides insights into the intricate interactions governing telomere maintenance.
• Understanding these conserved mechanisms is vital for research into telomere biology and related diseases.