INVESTIGADORES
MARTINEZ TOSAR Leandro Julian
congresos y reuniones científicas
Título:
Staufen Cytoplasmic Granules in mRNA Targeting and Translation
Autor/es:
M.G. THOMAS L.J. MARTINEZ TOSAR, AND G.L.BOCCACCIO
Lugar:
Iguazú Falls, Misiones Argentina
Reunión:
Simposio; Symposium Gene Expression & RNA Processing; 2003
Resumen:
<!--
/* Font Definitions */
@font-face
{font-family:"Cambria Math";
panose-1:2 4 5 3 5 4 6 3 2 4;
mso-font-charset:0;
mso-generic-font-family:roman;
mso-font-pitch:variable;
mso-font-signature:-1610611985 1107304683 0 0 159 0;}
/* Style Definitions */
p.MsoNormal, li.MsoNormal, div.MsoNormal
{mso-style-unhide:no;
mso-style-qformat:yes;
mso-style-parent:"";
margin:0cm;
margin-bottom:.0001pt;
mso-pagination:widow-orphan;
font-size:12.0pt;
mso-bidi-font-size:10.0pt;
font-family:"Arial","sans-serif";
mso-fareast-font-family:"Times New Roman";
mso-bidi-font-family:"Times New Roman";
mso-ansi-language:ES;
mso-fareast-language:ES;}
.MsoChpDefault
{mso-style-type:export-only;
mso-default-props:yes;
font-size:10.0pt;
mso-ansi-font-size:10.0pt;
mso-bidi-font-size:10.0pt;}
@page Section1
{size:612.0pt 792.0pt;
margin:70.85pt 3.0cm 70.85pt 3.0cm;
mso-header-margin:36.0pt;
mso-footer-margin:36.0pt;
mso-paper-source:0;}
div.Section1
{page:Section1;}
-->
Cytoplasmic
mRNA Granules are the functional unit for a variety of post-transcriptional
events such as mRNA transport, silencing, activation and degradation. The
double-stranded RNA-binding protein Staufen is an RNA granule-forming protein
involved in asymmetric distribution of mRNAs in Drosophila´s developing CNS and oocytes. Two highly homologous
genes, Staufen 1 and Staufen 2, exist in vertebrates. We isolated several
Staufen 1 splicing variants, one of them being a minor transcript and potential
target of the Non-sense Mediated Decay surveillance mechanism. Staufen 1 has
two putative nuclear localization signals and showed nuclear-cytoplasmic
localization. Nuclear export of Staufen 1 was CRM-1 and exportin 5-independent
in transienlty transfected cells. Specific antibodies against Staufen 1 and 2
were prepared to study these RNA-binding proteins in myelinating rodent
oligodendrocytes by imaging and biochemical approaches. Sedimentation velocity
gradient analysis of oligodendrocyte cytosolic extracts showed that Staufen
comigrates mostly with polysomes. Upon treatment of cultured cells with
puromycin, Staufen 1 granules partially coalesced in larger structures devoid
of ER membranes and reminiscent of stress granules, thus indicating the
association of Staufen with actively elongating polysomes and suggesting a role
in translation. Confocal microscopy analysis of Staufen 1 and Staufen 2
subcellular distribution indicated that these molecules define two distinct
populations of 400-800 nm-sized granules at the oligodendrocyte´s processes. We
evaluated the colocalization of Staufen proteins with the prototype
myelin-targeted MBP mRNA. This messenger was also present in granules with
similar size distribution and abundance. The majority (80%) of MBP mRNA
granules were negative for both Staufen 1 and 2. Altogether these results
suggest the existence of specialized RNA complexes involved in
post-transcriptional regulation at the myelin compartment. Interference
experiments against specific Staufen molecules will be carried out to
investigate their potential role in packaging, targeting, anchoring or
translation.
