Telomerase is a unique RNA-containing reverse transcriptase that synthesizes the 3’-end of
telomeres. It is a highly regulated determinant of tumorigenesis, cellular aging, and stem cell
renewal. All telomerases contain a catalytic core comprising telomerase reverse transcriptase
(TERT) and telomerase RNA (TER), along with other proteins involved in biogenesis, assembly,
and activation. TER has an integral template complementary to ~1.5 telomere repeats used by
TERT to repetitively synthesize the telomere repeat (TTGGGG in Tetrahymena and TTAGGG in
human), but this template alone is insufficient for activity with TERT. Our interest in telomeres
and telomerase began in the 1990’s when we studied the structure of telomeric repeat
sequences, using NMR to determine the first G-quadruplex structures. For the past decade, we
have been using an integrative structural biology approach combining NMR, X-ray
crystallography, and electron microscopy to study the structure and function of Tetrahymena
and human telomerase. I will discuss how our NMR studies of telomerase RNA structure and
dynamics, X-ray crystal structures of protein-TER complexes, and cryo electron microscopy of
the holoenzyme have together helped reveal the structure, function, and interactions of this
remarkable enzyme.
Juli Feigon (University of California)