The Questions of Developmental Biology

One of the most remarkable ways of regulating
the translation of a specific message is seen in
Caenorhabditis elegans. This nematode lives up to its
name, having evolved a particularly elegant solution to
the problem of controlling larval gene expression
(Lee et al. 1993; Wightman et al. 1993).
It makes a naturally occuring antisense mRNA to one
of its own messages. High levels of the LIN-14
transcription factor are important in the development of
early larval organs. Thereafter, the LIN-14 protein is no
longer seen, although lin-14 messages can be detected
throughout development. C. elegans is able to inhibit
the synthesis of LIN-14 from these messages by
activating the lin-4 gene. The lin-4 gene does not
encode a protein. Rather, it encodes two small RNAs
(the most abundant being 25 nucleotides long, the other
continuing for 40 more nucleotides) that are
complementary to an imperfectly repeated site in the
lin-14 3´ UTR. Figure 5.32 shows a hypothetical sketch
of what might be happening. It appears that the binding
of the lin-4 transcripts to the lin-14 mRNA 3´ UTR
does not signal the destruction of the message, but
rather prevents the message from being translated.
Control of RNA expression by cytoplasmic localization
Not only is the time of mRNA translation regulated, but so is the place of RNA
expression. Just like the selective repression of mRNA translation, the selective localization of
messages is also often accomplished through their 3´ UTRs, and it is also often performed in
oocytes. Rebagliati and colleagues (1985) showed that there are certain
mRNAs in Xenopus embryos that are selectively transported to the
vegetal pole of the frog oocyte (Figure 5.33). After fertilization, these
messages make proteins that are found only in the vegetal blastomeres.
In Drosophila, the bicoid and nanos messages are each localized to
different ends of the oocyte. The 3´ UTR of the bicoid mRNA allows
this message to bind to the microtubules through its association with
two other proteins (swallow and staufen). If the bicoid 3´ UTR is
attached to some other message, that mRNA also will be bound to the
anterior pole of the oocyte (Driever and Nüsslein-Volhard 1988a, b;
Ferrandon et al. 1994). The 3´ UTR of the nanos message similarly
allows it to be transported to the posterior pole of the egg, where it will be bound to the
cytoskeleton (Gavis and Lehmann 1994).
As we saw in Chapter 3, this localization
allows the Bicoid protein to form a gradient
wherein the highest amount of it is at the anterior
pole, while the Nanos protein forms a gradient
with its peak at the posterior pole (Figure 5.34).
The ratio of these two proteins will eventually