The Questions of Developmental Biology

compensation in mammals, as well as in other animals that have chromosomal sex determination.
*Lee and Lu (1999) provide a fascinating clue to Xist regulation. They have shown that Xist may be regulated by a
natural antisense RNA that binds to it. This RNA (called Tsix) is transcribed from the X chromosome that remains
active
Differential RNA Processing
The regulation of gene expression is not confined to the differential transcription of
DNA. Even if a particular RNA transcript is synthesized, there is no guarantee that it will create a
functional protein in the cell. To become an active protein, the RNA must be (1) processed into a
messenger RNA by the removal of introns, (2) translocated from the nucleus to the cytoplasm,
and (3) translated by the protein-synthesizing apparatus. In some cases, the synthesized protein is
not in its mature form and (4) must be posttranslationally modified to become active. Regulation
can occur at any of these steps during development.
The essence of differentiation is the production of different sets of proteins in different
types of cells. In bacteria, differential gene expression can be effected at the levels of
transcription, translation, and protein modification. In eukaryotes, however, another possible level
of regulation exists namely, control at the level of RNA processing and transport. There are two
major ways in which differential RNA processing can regulate development. The first involves
the "censoring" of which nuclear transcripts are processed into cytoplasmic messages. Here,
different cells can select different nuclear transcripts to be processed and sent to the cytoplasm as
messenger RNA. The same pool of nuclear transcripts can thereby give rise to different
populations of cytoplasmic mRNAs in
different cell types (Figure 5.26A).
The second mode of differential RNA
processing is the splicing of the mRNA
precursors into messages for different
proteins by using different
combinations of potential exons.
If an mRNA precursor had five
potential exons, one cell might use
exons 1, 2, 4, and 5; a different cell
might utilize exons 1, 2, and 3; and yet
another cell type might use yet another
combination (Figure 5.26B).
Thus, one gene can create a family of
related proteins.
Control of early development by nuclear RNA selection
In the late 1970s, numerous investigators found that mRNA was not the primary
transcript from the genes. Rather, the genes transcribed nuclear RNA (nRNA), sometimes called
heterogeneous nuclear RNA (hnRNA) or pre-messenger RNA (pre-mRNA). This nRNA is
usually many times longer than the messenger RNA because the nuclear RNA contains introns
that get spliced out during the passage from nucleus to cytoplasm. Originally, investigators
thought that whatever RNA was transcribed in the nucleus was processed into cytoplasmic
mRNA. But studies of sea urchins showed that different cell types could be transcribing the same
type of nuclear RNA, but processing different subsets of this population into mRNA in different