Flipping through the latest issue of Cell:
Ujwal Sheth from Roy Parker's lab details the molecular mechanism that targets RNAs with premature stop codons to processing-bodies (or p-bodies) via the non-sense mediated decay (NMD) pathway. P-bodies are dense cytoplasmic granule-like structures that serve as sites of mRNA storage/degradation. P-bodies contain decapping enzymes, RNAses, and many other proteins of unkown function. In this paper the authors demonstrate that the NMD component, and RNA helicase, Upf1p, targets aberrant mRNA to granules. Upf1p's ATPase activity is then required to recruit Upf2p and Upf3p to p-bodies.
It remains unclear how premature stop codons are recognized in yeast. In higher eukaryotes, if a stop codon occurs before a splice site, ribosomes fall off the RNA before they can kick off exon junction complexes that mark sites along the RNA where splicing has occurred. The exon junction complex then recruits NMD components that target the mRNA for destruction.
There has been much fuss lately with these p-bodies and the related structures termed "stress granules". Both structures are seen in most eukaryotes and play several seemingly incompatible roles. In general non-translating cytosolic mRNAs are shuffled into these structures. But why?
Some facts about RNA bodies:
- these cytosolic structures do not contain membranes yet are very dense and exclude large proteins
- much of the maternal RNA in oocytes is stored in granules
- a related structure, termed simply "RNA granules", transport RNA up dendrites in neurons
- stress granules are thought to be formed by the aggregation of TIA1, a protein thought to have prion activities
- neuronal RNA granules are thought to be regulated by CPEB (Cytioplasmic Polyadenylation Element Binder), another protein thought to have prion properties
- RNAi components target RNAs to p-bodies, and proteins involved in RNAi are enriched in p-bodies
The question is, why pack RNA so tightly into dense structures? And why form these particles with aggregating prions? Prions can exist in several forms, so perhaps RNA granules must adapt several roles? Some RNA granules, such as those in neurons and oocytes store RNA (i.e. a precious cargo), but in other cases RNA granules act as trash compactors. I'm sure that this story will get more interesting in the coming months/years.
Cross posted at Science Sampler.