Identification and characterization of Npl3 as a novel prion like protein and its function in the regulation of gene expression in Saccharomyces cerevisiae
Bracho Rincon, Dina Paola
AdvisorGonzález-Vargas, Carlos I.
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Nuclear protein localization-3 (Npl3) is a highly dynamic protein involved in mRNA biogenesis. Previous studies showed that the npl3-95 allele encodes a protein that can aggregate into high molecular weight complexes. Besides, two different bioinformatics analysis scored Npl3 as a potential prion protein in yeast. Npl3 protein was characterized as a novel prion-like protein in Saccharomyces cerevisiae using genetic and biochemical criteria. Results presented in this doctoral dissertation show that; (1) Npl3 harbors a putative prion domain in its RGG domain, (2) the paromomycin sensitivity phenotype associated with the npl3-95 mutant allele is dominant and shows non-mendelian inheritance (cytoplasmic inheritance), (3) GndHCl treatment and HSP104 deletion eliminate the paromomycin sensitivity phenotype, and (4) over-expression of the Npl3 wild type protein induces prion-like aggregates. Interestingly, the presence of the Npl3 prion-like form confers the acquisition of an adenine prototrophy phenotype and a decrease in flocculation in the yeast Saccharomyces cerevisiae. Altogether, the results presented in this dissertation provide new evidence of the biological significance of yeast prions and their regulatory role in gene expression.