Silent no more: Expression of RNA from telomeres may regulate telomere length

Abstract

The ends of eukaryotic chromosomes are capped with telomeres, a protective structure needed to preserve genome integrity. The maintenance of telomeres is critical, as instability at the telomere is linked to cancer, and shortening is linked to cellular senescence. Long thought to be transcriptionally silent due to their heterochromatic nature, a recent publication by Schoeftner and Blasco found that a G-rich strand of RNA was transcribed from mammalian telomeres, and that the abundance of this nuclear RNA corresponded with telomere length 1. A second study from the Lingner laboratory also identified telomeric RNAs, and showed that non-sense mediated decay proteins negatively regulated their ability to form nuclear foci2. The Blasco paper revealed that telomeric RNAs (TelRNAs) were transcribed by RNA polymerase II, and also that the telomere binding protein TRF1 could interact with this polymerase. TelRNAs co-localized with TRF1 at telomeres, as well as other heterochromatic structures in the nucleus. The epigenetic status of the telomere contributed to TelRNA abundance, indicative of a dynamic relationship between the two. Finally, TelRNAs had the ability to regulate telomerase activity, demonstrated in an in-vitro assay. The identification and characterization of TelRNAs adds to the list of factors controlling telomere length and stability, and also increases our understanding of how these critical components of chromosomes operate in the cell and how they contribute to cancer and aging.