A nucleolar protein allows viability in the absence of the essential ER-residing molecular chaperone calnexin

In fission yeast, the ER-residing molecular chaperone calnexin is normally essential for viability. However, a specific mutant of calnexin that is devoid of chaperone function (hcd Cnx1p) induces an epigenetic state that allows growth of Schizosaccharomyces pombe without calnexin. This calnexin-independent (Cin) state was previously shown to be mediated via a non-chromosomal element exhibiting some prion-like features. Here, we report the identification of a gene whose overexpression induces the appearance of stable Cin cells. This gene, here named cif1⁺ for calnexin-independence factor 1, encodes an uncharacterized nucleolar protein. The Cin cells arising from cif1⁺ overexpression (Cin_cif1 cells) are genetically and phenotypically distinct from the previously characterized Cin_{hcd cnx1} cells, which spontaneously appear in the presence of the hcd Cnx1p mutant. Moreover, cif1⁺ is not required for the induction or maintenance of the Cin_{hcd cnx1} state. These observations argue for different pathways of induction and/or maintenance of the state of calnexin independence. Nucleolar localization of Cif1p is required to induce the Cin_cif1 state, thus suggesting an unexpected interaction between the vital cellular role of calnexin and a function of the nucleolus.