Telomerase contains a large RNA subunit, TER, and a protein catalytic subunit, TERT. Whether telomerase functions as a monomer or dimer has been a matter of debate.
The laboratories of Prof Daniela Rhodes, Asst/Prof Sara Sandip (School of Biological Sciences, NTU) and their collaborator Prof Joachim Lingner (Ecole Polytechnique Fédérale de Lausanne, Switzerland) published today in Nature Structural & Molecular Biology (March 10, 2013) biochemical and labeling data that show, that in vivo–assembled human telomerase contains two TERT subunits and binds two telomeric DNA substrates. Notably, catalytic activity requires both TERT active sites to be functional, which demonstrates that human telomerase functions as a dimer. They also present the three-dimensional structure of the active full-length human telomerase dimer, determined by single-particle EM in negative stain.
Telomerase has a bilobal architecture with the two monomers linked by a flexible interface. The monomer reconstruction at 23 Å resolution and fitting of the atomic structure of the TERT subunit from beetle Tribolium castaneum reveals the spatial relationship between RNA and protein subunits, providing insights into telomerase architecture.
Sauerwald A, Sandin S, Cristofari G, Scheres SHW, Lingner J, Rhodes D. (2013) Structure of active dimeric human telomerase. Nature Structural & Molecular Biology. doi:10.1038/nsmb.2530