| Prions are most often associated with pathogenic protein misfolding, infectious amyloid aggregates and fatal neurodegenerative diseases. However, there exist in Saccharomyces cerevisiae multiple proteins capable of adopting heritable prion conformations without resulting in any pathology to the cell. Lsm4p is an essential splicing factor that has an additional role as an activator of mRNA decapping. It was isolated in a screen for yeast prions based on homology to Q/N-rich "prion domain" sequences and functional interaction with the yeast prion [PSI +]. Lsm4p is involved in important cellular processes and functions in organized protein complexes, such as the spliceosome and P-bodies, making it an attractive candidate to study as a potentially functional prion. Our studies show that Lsm4p formed aggregates with prion-like properties, including protease-resistance, heritability and the ability to organize into amyloid fibers. Lsm4p aggregation was enhanced by the presence of other prions and severely abrogated in the absence of the chaperone Hsp104. The aggregation of Lsm4p caused a mild growth defect and a redistribution of foci indicative of P-bodies. Cells that had been exposed to 4°C were more prone to Lsm4p aggregation. Together, this provides evidence that Lsm4p can indeed adopt a heritable, stable protein conformation that shares many properties with other yeast prions. |
