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rise to an asymmetric distribution of factors, creating in turn polarized cells [61].
This polarity has important consequences in many processes, such as development,
differentiation, cell motility and neuron functionality. Different means are used to
reach this goal but the most effective seems to be RNA localization associated with
local translation to generate proteins only in the targeted area. The elements
required for the localization are sequences in cis on the RNA, called zipcodes
or Localization Elements (LEs), and the trans-acting factors recognizing and binding
them [62
64]. Examples are: the
b
-actin localization zipcode [65
67] and its trans-
-
-
acting factor, ZBP1 [68, 69] in
fibroblasts; Vg1 LE with hnRNP I, Vera and 40 LoVe in
Xenopus oocytes [70
73]; the A2RE signal in the Myelin Basic Protein (MBP) with
hnRNP A2 in neurons [13, 74] and the ASH1 zipcode with She2p in yeast S.
cerevisiae [21, 75, 76]. In general, localizing mRNAs are shuttled to speci
c areas of
the cell or the oocyte along cytoskeletal elements such as microtubules or actin
filaments. They seem to be actively translocated by motor proteins of the myosin,
kinesin and dynein families. A corollary of localization is that the mRNA must be
translationally repressed during its movement. A number of trans-acting factors
mediate translational repression by binding the RNA directly (ZBP1,
-
[77];
Puf6p, [78]; Khd1p, [79, 80]).
8.4.2.1 Some Examples of Localization in Mammalian Cells and Drosophila
Localization is particularly important during development. The most characterized
cellular systems to study RNA localization in mammalian cells are migrating
fibroblasts, oligodendrocytes and neurons. In
fibroblasts
-actin mRNAs are local-
ized at the leading edge of the cell, a fact that correlates with the requirement of high
protein levels for actin polymerization during cell movement. The complex of
mRNA, ZBP1 and ZBP2 assembled in the nucleus [81] moves in the cytoplasm
along actin
laments probably carried by amyosinmotor [82, 83] to be anchored at the
leading edge possibly by EF1
b
[84] where it is
finally translated.
Neurons and oligodendrocytes are also a class of highly polarized cells since
many mRNAs typically travel from the cell body to the extremities in dendrites and
axons. RNAs travel in granules that may contain many copies of an mRNA or several
types of mRNA. All this traf
a
cking moves on cytoskeleton elements by motors: MBP
mRNA is probably associated with microtubules through a kinesin [85]. The same
motor is also responsible for the CamKII
targeting in hippocampal dendrites [86]
and tau mRNA in axons [87]. Moreover in neurons,
a
-actin is localized in the growth
cone by ZBP1 along microtubules. Since the same motor can drive the movement
of different RNAs, the recruitment of speci
c adaptors and RNA binding proteins
in the locasome will allow the selection of the
nal address for the speci
c cargo in
the complex.
During development, localization mechanisms are also used by Drosophila cells to
create mRNA gradients, and consequently protein gradients, indispensable for
generating speci
c patterns of expression essential for development of the oocyte
and the embryo. One of the
first determinants breaking the initial symmetry of the
oocyte is gurken mRNA. It is involved in the speci
cation of both the anterior
-
posterior and the dorsal
-
ventral axis by two rounds of signals at different times
b
