Regulation of Cell Polarity and RNA Localization in Vertebrate Oocytes - International Review of Cell and Molecular Biology - page 148

translational regulation are often mechanistically linked. In line with this
idea, gdf1 is translated only after vegetal cortex localization is complete
( Dale et al., 1989; Tannahill and Melton, 1989; Wilhelm et al., 2000 ).
Gdf1 translation is normally inhibited by an 350 nt element downstream

from the localization element ( Wilhelm et al., 2000 ). Interestingly, KH-type
splicing regulatory protein (Khsrp/Gdf1RBP71/Fbp2; Kroll et al., 2002 ),
which binds to the gdf1 LE, was found to control an atypical mechanism
for regulating gdf1 translation ( Kolev and Huber, 2003 ). Khsrp binding to
the LE stimulates cleavage of gdf1 RNA at a canonical polyadenylation
sequence, resulting in removal of the inhibitory element ( Kolev and
Huber, 2003 ). Khsrp has RNA duplex strand separation activity in vitro ,
suggesting that it may remodel gdf1 -associated RNP complexes to allow
access of cleavage-related proteins ( Kolev and Huber, 2003 ).
Elavl2 (Elav-like 2/Elrb/Hu antigen B), a member of the conserved
Embryonic lethal, abnormal vision family of RNA-binding proteins, binds
to the gdf1 translational repression element ( Colegrove-Otero et al., 2005 )
and is a good candidate for inhibiting gdf1 translation in vivo . Blocking anti-
body injections into midoogenesis stage oocytes results in precocious Gdf1
translation ( Colegrove-Otero et al., 2005 ). Khsrp protein accumulates only
in late stage oocytes and correlates with Gdf1 protein levels ( Kolev and
Huber, 2003 ), suggesting that gdf1 translation is controlled temporally,
and not by its localization per se . However, other mechanisms directly
linking translation to completion of localization and anchoring have not
been ruled out.

3.1.2 Localization of vegt RNA
Localization mechanisms of a second late pathway transcript, vegt , have also
been characterized and are highly similar to that of gdf1 ( Bubunenko et al.,
2002; Kwon et al., 2002 ). Vegt localization during oogenesis follows the
same pattern as gdf1 ( Lustig et al., 1996; Stennard et al., 1996; Zhang and
King, 1996 ). Deletion mapping defined a

300-nt vegt localization element
in the 3 0 -UTR, which also contained clusters of UUCAC motifs
( Bubunenko et al., 2002; Kwon et al., 2002 ). These motifs are both neces-
sary and sufficient for Igf2bp3 binding and vegetal localization ( Bubunenko
et al., 2002; Kwon et al., 2002 ). Furthermore, the vegt LE and the gdf1 LE
can functionally compete with each other in oocytes and biochemically,
suggesting that they share the same trans -acting proteins ( Kwon et al., 2002 ).
Binding of other localized RNA-associated proteins to vegt has also been
demonstrated, including Dazap1, Khsrp, and Hnrnpab ( Kroll et al., 2009;