Telomeric Repeat-Containing RNA: Biogenesis, Regulation, and Functions

Telomeric repeat-containing RNA (TERRA) molecules are transcripts comprising extended stretches of telomeric G-rich repeats, which are generated from telomeres or intrachromosomal loci. TERRA production is an evolutionarily conserved process observed across all eukaryotic kingdoms. While originally thought to localize and function only at telomeres, it is now clear that TERRA is involved in numerous cellular pathways beyond telomere maintenance, including gene expression regulation and signaling of dysfunctional telomeres to the cytoplasm and the extracellular environment. In this work, we will review key aspects of TERRA biogenesis, regulation, and functional relevance and propose models to reconcile the multiple and sometimes contradictory functions ascribed to TERRA. Based on TERRA interaction with proteins involved in disparate cellular processes, we also suggest that the full spectrum of TERRA-associated functions is still far from being completely unveiled. We anticipate that further study of this complex and fascinating RNA will reveal additional surprises in the future.