Эукариотикалық жасушалардағы mRNA және РНҚ байланыстырушы ақуыздардың биомолекулалық конденсаты (P денелері)

Biomolecular condensates of mRNA and RNA binding proteins found in eukaryotic cells

In cellular biology, P bodies, or processing bodies, are distinct foci formed by phase separation within the cytoplasm of a eukaryotic cell consisting of many enzymes involved in mRNA turnover. P bodies are highly conserved structures and have been observed in somatic cells originating from vertebrates and invertebrates, plants and yeast. To date, P bodies have been demonstrated to play fundamental roles in general mRNA decay, nonsense mediated mRNA decay, adenylate uridylate rich element mediated mRNA decay, and microRNA (miRNA) induced mRNA silencing. Not all mRNAs which enter P bodies are degraded, as it has been demonstrated that some mRNAs can exit P bodies and re initiate translation. Purification and sequencing of the mRNA from purified processing bodies showed that these mRNAs are largely translationally repressed upstream of translation initiation and are protected from 5' mRNA decay. Later work called this into question suggesting P bodies store mRNA until needed for translation. In neurons, P bodies are moved by motor proteins in response to stimulation. This is likely tied to local translation in dendrites.

P bodies were first described in the scientific literature by Bashkirov et al. in 1997, in which they describe "small granules discrete, prominent foci" as the cytoplasmic location of the mouse exoribonuclease mXrn1p. It wasn’t until 2002 that a glimpse into the nature and importance of these cytoplasmic foci was published., when researchers demonstrated that multiple proteins involved with mRNA degradation localize to the foci. Their importance was recognized after experimental evidence was obtained pointing to P bodies as the sites of mRNA degradation in the cell. The evidence being that GW182 and Ago2, both associated with miRNA gene silencing, are found exclusively in multivesicular bodies or GW bodies and are not localized to P bodies. Also of note, P bodies are not equivalent to stress granules and they contain largely non overlapping proteins.

microRNA mediated repression occurs in two ways, either by translational repression or stimulating mRNA decay. miRNA recruit the RISC complex to the mRNA to which they are bound. The link to P bodies comes by the fact that many, if not most, of the proteins necessary for miRNA gene silencing are localized to P bodies, as reviewed by Kulkarni et al. (2010). These proteins include, but are not limited to, the scaffold protein GW182, Argonaute (Ago), decapping enzymes and RNA helicases. The current evidence points toward P bodies as being scaffolding centers of miRNA function, especially due to the evidence that a knock down of GW182 disrupts P body formation. However, there remain many unanswered questions about P bodies and their relationship to miRNA activity. Specifically, it is unknown whether there is a context dependent (stress state versus normal) specificity to the P body's mechanism of action. Based on the evidence that P bodies sometimes are the site of mRNA decay and sometimes the mRNA can exit the P bodies and re initiate translation, the question remains of what controls this switch. Another ambiguous point to be addressed is whether the proteins that localize to P bodies are actively functioning in the miRNA gene silencing process or whether they are merely on standby.