Prions, amyloids, and RNA: Pieces of a puzzle

Abstract

Amyloids are protein aggregates consisting of fibrils rich in β-sheets. Growth of amyloid fibrils occurs by the addition of protein molecules to the tip of an aggregate with a concurrent change of a conformation. Thus, amyloids are self-propagating protein conformations. In certain cases these conformations are transmissible / infectious; they are known as prions. Initially, amyloids were discovered as pathological extracellular deposits occurring in different tissues and organs. To date, amyloids and prions have been associated with over 30 incurable diseases in humans and animals. However, a number of recent studies demonstrate that amyloids are also functionally involved in a variety of biological processes, from biofilm formation by bacteria, to long-term memory in animals. Interestingly, amyloid-forming proteins are highly overrepresented among cellular factors engaged in all stages of mRNA life cycle: from transcription and translation, to storage and degradation. Here we review rapidly accumulating data on functional and pathogenic amyloids associated with mRNA processing, and discuss possible significance of prion and amyloid networks in the modulation of key cellular functions.

Keywords: Amyloid; CPEB; Prion; Pub1; S. cerevisiae; Sup35; Tia1; yeast.

FIGURE 1.

RNA-modulating prions and amyloids, and cellular processes in which they are implicated. Shown are cellular processes or protein complexes, which are associated with corresponding prions and amyloids. Arrows connect consequent stages of the mRNA life cycle.

FIGURE 2.

Q/N-rich subunits of protein complexes in S. cerevisiae and their interactions. Shown is the interactome of Q/N-rich subunits of protein complexes containing more than one Q/N-rich subunit. Lines indicate physical protein-protein interactions (according to data from “String” database, http://string-db.org/). Experimentally proven prion and amyloid-forming proteins are indicated by black circles, while other Q/N-rich proteins are indicated by gray circles. Light gray rectangles indicate corresponding protein complexes (including their names, as indicated).