Creative catalysis: pieces of the RNA world jigsaw.

found to be a minor component of amyloid plaques in Alzheimer's disease [19]. Alternatively, it is possible that there is an inhibitor of prion generation and propagation whose activity is inhibited by an excess of another prion. Excess Hsp104p cures [PSI + ] [20], excess Ydj1p (an Hsp40) can cure [URE3] [21], and Sis1p (another Hsp40) cures [RNQ + ] [22]. Overexpression of Ssb members of the Hsp70 family promote curing by Hsp104 [23]. Amyloid or aggregates of one overproduced protein could tie-up one or more of these factors, preventing their anti-prion action and accounting for the Pin + phenotype. Distinguishing these two models will not be easy, but it seems likely that continued study of the yeast models of amyloidosis and prion diseases will open new ideas and approaches to these difficult human diseases. allowing ureidosuccinic acid uptake in yeast. Evidence for a prion analog in S. cerevisiae: the [URE3] non-Mendelian genetic element as an altered URE2 protein. Guanidine hydrochloride inhibits Hsp104 activity in vivo: a possible explanation for its effect in curing yeast prions. The elimination of the yeast [PSI+] prion by guanidine hydrochloride is the result of Hsp104 inactivation.inducing domain of yeast Ure2p and protease resistance of Ure2p in prion-containing cells. omnipotent suppressor gene is involved in the maintenance of the non-Mendelian determinant [psi+] in the yeast Saccharomyces cerevisiae. Multiple Gln/Asn-rich prion domains confer susceptibility to induction of the yeast [PSI+] prion. Prion-inducing domain 2-114 of yeast Sup35 protein transforms in vitro into amyloid-like filaments. [URE3] prion propagation in Saccharomyces cerevisiae: requirement for chaperone Hsp104 and curing by overexpressed chaperone Ydj1p. Evidence for a protein mutator in yeast: role of the Hsp70-related chaperone Ssb in formation, stability and toxicity of the [PSI+] prion. Novel ribozymes produced by in vitro selection techniques provide insights into the possible mechanisms of protein synthesis evolution. The availability of such ribozymes also paves the way for experiments to explore the evolution of RNA–protein enzymes. One of the biggest paradigm shifts in the field of biochemistry in the 20th century resulted from the discovery of RNA enzymes (ribozymes). The series of classic experiments involving Tetrahymena pre-rRNA helped to confirm the importance of ribozymes in cellular RNA processing [1–3] and lent increased credibility to the RNA world hypothesis [4]. In this envisioned world, RNA served both as the genetic material and the principal cellular enzyme, and was probably assisted in the latter role by …