The [KIL-d] Element Specifically Regulates Viral Gene Expression in Yeast

Abstract

The cytoplasmically inherited [KIL-d] element epigenetically regulates killer virus gene expression in Saccharomyces cerevisiae. [KIL-d] results in variegated defects in expression of the M double-stranded RNA viral segment in haploid cells that are “healed” in diploids. We report that the [KIL-d] element is spontaneously lost with a frequency of 10−4–10−5 and reappears with variegated phenotypic expression with a frequency of ≥10−3. This high rate of loss and higher rate of reappearance is unlike any known nucleic acid replicon but resembles the behavior of yeast prions. However, [KIL-d] is distinct from the known yeast prions in its relative guanidinium hydrochloride incurability and independence of Hsp104 protein for its maintenance. Despite its transmissibility by successive cytoplasmic transfers, multiple cytoplasmic nucleic acids have been proven not to carry the [KIL-d] trait. [KIL-d] epigenetically regulates the expression of the M double-stranded RNA satellite virus genome, but fails to alter the expression of M cDNA. This specificity remained even after a cycle of mating and meiosis. Due to its unique genetic properties and viral RNA specificity, [KIL-d] represents a new type of genetic element that interacts with a viral RNA genome.

RNA viruses, M satellites, chromosomal killer genes, and killer/nonkiller phenotypes in the 100-genomes S. cerevisiae strains

“…Unlike fully functional K + R + M satellites, mutant M satellites may encode partially functional or nonfunctional killer toxin (K ± or K − , respectively) and functional killer toxin–specific resistance (R + ) functions ( Talloczy et al . 1998 , 2000 ; Suzuki et al . 2015 ).…”

“…First, the K − phenotypes of 1 or both backgrounds may be [Kil-d]/M satellite genotype ( Talloczy et al . 1998 2000 ; Suzuki et al . 2015 ) or nuclear genotype dependent (e.g.…”

“…While the mutation rates for S. cerevisiae RNA viruses are not known, there is strong evidence that the mutation/loss rates for M satellites are high due, for example, to the prion-like [KIL-d] element ( Talloczy et al . 1998 , 2000 ; Suzuki et al . 2015 ).…”