Creating a protein-based element of inheritance.
Proteins capable of self-perpetuating changes in conformation and function (known as prions) can serve as genetic elements. To test whether novel prions could be created by recombinant methods, a yeast prion determinant was fused to the rat glucocorticoid receptor. The fusion protein existed in different heritable functional states, switched between states at a low spontaneous rate, and could be induced to switch by experimental manipulations. The complete change in phenotype achieved by transferring a prion determinant from one protein to another confirms the protein-only nature of prion inheritance and establishes a mechanism for engineering heritable changes in phenotype that should be broadly applicable.
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Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, 5841 South Maryland Avenue MC1028, Chicago, IL 60637, USA.
Lindquist
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D000818:Animals; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D019791:Guanidine / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000494:pharmacology; D010454:Peptide Termination Factors; D010641:Phenotype; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic; D014170:Transformation, Genetic
D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D010454:Peptide Termination Factors; D011328:Prions; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D019791:Guanidine