The Telomere Shortening Signal May Be Explained by a Fountain Mechanism Modulating the Expression of Eukaryotic Genes

We propose a possible mechanism for the telomere shortening signal. The suggested solution of this as yet unsolved enigma—how cell senescence is causally linked to telomere shortening—is based on a "fountain theory" of modulation of eukaryotic gene expression, in which gene expression is modulated by ionic channels of the inner nuclear membrane. These Ca²⁺ and Zn²⁺ channels are opened transiently through the action of a special small nuclear RNA (the fountain RNA or fRNA) on the ionic channels as conformational changes of the fRNA and channel-forming protein occur. Specific Ca²⁺ and Zn²⁺ ion channels allow these ions to pass from the perinuclear lumen to the nucleoplasmic gene surroundings. The resultant change of ionic concentration in close vicinity to certain genes, in turn, will alter some intranuclear processes and properties (e.g., mRNA stability, transcript maturation, chromatin configuration, transcriptional activity, and so forth).

Such fRNA-dependent ionic "fountains," may serve as a major mechanism regulating quantitative gene (phenotypic) expression in eukaryotes. We suggest that among metal-activated transcription factors, zinc-finger nuclear proteins evolved, and they are used in the nucleus as an alternative, noncalcium, path of gene-activity modulation, by means of fRNA-dependent channels, increasing the versatility of a fountain system.