DYNAMIC CONVERSION OF RNA GRANULES INTO STRESS GRANULES

M. GABRIELA THOMAS,; CLAUDIA C. LEISHMAN,; JORGE CORREALE; GRACIELA L. BOCCACCIO.

Pinamar, Argentina

Congreso; XLI reunión SAIB; 2005

Cytosolic mRNA granules are the functional units for mRNA transport, silencing, activation and degradation. Staufen, FMRP, SMN and other RNA-binding proteins are conserved markers of distinct RNA granules. When exposed to stress conditions, eucariotic cells built up larger RNA-protein aggregates, known as stress granules (SGs). SGs are transient structures that contain housekeeping mRNAs which are not translated during the stress response. We found that SMN, FMRP and Staufen RNA granules are plastic, respond to the cellular translational state and can be converted into SGs upon different stressors. SGs formation involves the remodeling of normal RNA granules as SGs include Poly(A)-binding protein (PABP), the RNA-binding proteins HuR and TIAR/TIA-1, and small but not large ribosomal subunits. We also analyzed the relationship between SGs and Processing Bodies (PB), cytosolic structures involved in mRNA decay. We found that the PB-components exoribonuclease Xrn1 and GW182 are recruited into SGs whereas the decapping enzyme Dcp1 is not. Upf1, a component of the SMD and NMD pathways, is also present in SGs. Our results suggest an equilibrium between RNA granules, polysomes, SGs and PBs that is modulated to help post-transcriptional regulation of the genome. Supported by NIH and Wadsworth Foundation (USA), and ANPCyT  and FLENI (Argentina)