INVESTIGADORES
MARTINEZ TOSAR Leandro Julian
congresos y reuniones científicas
Título:
Dynamic conversion of cytoplasmic RNA granules into stress granules
Autor/es:
THOMAS MG; MARTINEZ TOSAR LJ; BAEZ MV; LOSCHI M; DESBATS MA; LEISHMAN CC AND BOCCACCIO GL.
Lugar:
Banff, Canada
Reunión:
Conferencia; Tenth Annual Meeting of the RNA SOCIETY; 2005
Institución organizadora:
RNA Society
Resumen:
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Cytosolic
RNA granules packing mRNAs occur throughout evolution from insect oocytes to
mammalian oligodendrocytes and neurons. FMRP, Staufen, SMN, Smaug and other RNA
binding proteins (RBPs) are conserved components of RNA granules. We found
different RBPs residing in distinct RNA granule populations, likely containing
particular sets of mRNAs that are controlled coordinately with respect to their
subcellular localization, activation or decay. When exposed to stress
conditions, eukaryotic cells are able to build up a different kind of
RNA-protein aggregates of larger size, known as stress granules (SGs). SGs
transiently harbor cellular mRNAs silenced during the stress response. TIA1 and
TIAR, which in normal conditions are localized in the nucleus, concentrates in
these structures. We found that both cap binding proteins eIF4E and CBP80,
being the latter associated to mRNAs in their pioneer translation rounds, are
present in SGs. Normal cytoplasmic granules and SGs are different from
degradation foci identified by GW182 staining. RNA granules containing
ribosomes and SMN, FMRP, Staufen or Smaug are plastic, they depend on the
cellular translation activity and are converted into SGs upon different
stressors. Downregulation by siRNA of granule-forming RBPs inhibits SG
formation. A remodelling of normal RNA granules occurs during SG formation, as
these include TIA1 and TIAR and exclude large ribosomal subunits. In addition,
intracellular repositioning occurs, the disperse distribution of normal
granules turning into a more perinuclear localization in SGs. Both microtubules
and microfilaments are involved, as disruption of these cytoskeleton structures
impairs SG assembly. Kinetic analysis shows a stereotypical time course of SG
formation with a sequential recruitment of components. It remains to be
determined which are the signal transduction pathways regulating the conversion
of normal RNA granules into SGs; what are the cellular mechanisms controlling
the retrograde transport of RNPs, and how is the normal distribution of mRNPs
recovered after relief of the stress conditions.
