 |
M.A. Andrei, D. Ingelfinger,
R. Heintzmann, T. Achsel, R. Rivera-Pomar, & R. Lührmann
(2005) A role for eIF4E and eIF4E-transporter in targeting mRNPs
to mammalian processing bodies. RNA 11, 717-727. |
 |
http://www.rnajournal.org/cgi/content/abstract/11/5/717 |
A role for eIF4E and eIF4E-transporter
in targeting mRNPs to mammalian processing bodies
M. A. Andrei, D. Ingelfinger,R. Heintzmann,T. Achsel,
R. Rivera Pomar and R. Lührmann.
Department of Cellular Biochemistry and Department
of Molecular Biology, Max-Planck-Institute of Biophysical Chemistry, D-37077
Göttingen, Germany | IRCCS Fondazione Santa Lucia, Neurobiologia, 00179
Rome, Italy | Centro Regional de Estudios Genómicos (CREG), 1888-Florencio
Varela, Argentina
mRNP remodeling events required for the transition of an mRNA from active
translation to degradation are currently poorly understood. We identified
protein factors potentially involved in this transition, which are present
in mammalian P bodies, cytoplasmic foci enriched in 5' 3' mRNA degrading
enzymes. We demonstrate that human P bodies contain the cap-binding protein
eIF4E and the related factor eIF4E-transporter (eIF4E-T), suggesting novel
roles for these proteins in targeting mRNAs for 5' 3' degradation. Furthermore,
fluorescence resonance energy transfer (FRET) studies indicate that eIF4E
interacts with eIF4E-T and the putative DEAD box helicase rck/p54 in the
P bodies in vivo. RNAi-mediated knockdowns revealed that a subset of P
body factors, including eIF4E-T, LSm1, rck/p54, and Ccr4 are required
for the accumulation of each other and eIF4E in P bodies. In addition,
treatment of HeLa cells with cycloheximide, which inhibits translation,
revealed that mRNA is also required for accumulation of mRNA degradation
factors in P bodies. In contrast, knockdown of the decapping enzyme Dcp2,
which initiates the actual 5' 3' mRNA degradation did not abolish P body
formation, indicating it first functions after mRNPs have been targeted
to these cytoplasmic foci. These data support a model in which mRNPs undergo
several successive steps of remodeling and/or 3' trimming until their
composition or structural organization promotes their accumulation in
P bodies.
Keywords: mRNA degradation; translation; P bodies; eIF4E transporter