Nucleolar modulation of TRF1: A dynamic way to regulate telomere and cell cycle by nucleostemin and GNL3L

Abstract

Chromosomal ends are protected by a high-order structure called telomere.  Maintenance of correct telomere length and structure is critically important for the viability of both dividing and non-dividing cells.  Notably, targeted deletion of a component of the multi-protein telomere-capping complex, TRF1  (telomeric repeat binding factor 1), causes lethality at embryonic day 5-6 without apparent telomere deficiency,¹ raising the possibility that TRF1 may also moonlight outside the telomere.  Further reinforcing the extra-telomeric tie of TRF1, two studies from our group have reported the findings that TRF1 can be bound and modulated by two nucleolar GTP-binding proteins, nucleostemin (NS) and guanine nucleotide binding protein-like 3 (GNL3L), which exhibit apparently opposite effects on the protein degradation of TRF1.  In particular, GNL3L is able to stabilize TRF1 protein during mitosis and promote the metaphase-to-anaphase transition.  This manuscript extends the discussion on how this GNL3L-mediated TRF1 regulation creates a novel dynamic control on telomere and cell cycle, and extrapolates its evolutionary significance by contrasting the activities of NS and GNL3L.