Determining connections between nuclear and cytoplasmic mRNA events

We are interested in determining how events that affect nuclear mRNA biogenesis and processing can ultimately affect “downstream” cytoplasmic mRNA functions, and in particular the assembly and clearance of stress granules and P-bodies.

In particular, we have determined that the THO and TREX-2 complexes, which facilitate mRNA 3′ end processing and export, seem to smooth the entry of mature mRNPs into the cytoplasmic mRNA cycle. When these complexes are mutated, stress granule-like aggregates (“TT foci”) accumulate. TT foci share a similar protein and RNA composition to SGs, albeit with some protein differences, and like SGs are also targeted for autophagic clearance. Unlike SGs, they are non-dynamic structures based on insensitivity to cycloheximide. Thus, our working model is that TT foci are “dead ends” for improperly processed mRNPs that esacpe nuclear quality control mechanisms.

See Eshleman et al, RNA, 2016