TERRA, a Multifaceted Regulator of Telomerase Activity at Telomeres

In eukaryotes, telomeres are repetitive sequences at the end of chromosomes, which are maintained in a constitutive heterochromatin state. It is now known that telomeres can be actively transcribed, leading to the production of a telomeric repeat-containing noncoding RNA called TERRA. Due to its sequence complementarity to the telomerase template, it was suggested early on that TERRA could be an inhibitor of telomerase. Since then, TERRA has been shown to be involved in heterochromatin formation at telomeres, to invade telomeric dsDNA and form R-loops, and even to promote telomerase recruitment at short telomeres. All these functions depend on the diverse capacities of this lncRNA to bind various cofactors, act as a scaffold, and promote higher-order complexes in cells. In this review, it will be highlighted as to how these properties of TERRA work together to regulate telomerase activity at telomeres.