Biology Reference
In-Depth Information
Figure 6.2 Genetic and dynamic models for the heterochronic timing mechanism. The
top panel shows one model for the established genetic interactions of core players in
the timing mechanism indicating approximately when in developmental time they are
active. MicroRNA genes are boxed. Stage-specific fates are indicated by larval stage and
terminal differentiation by
“
diff.
”
The bottom panel represents the rising and falling
levels of the mature products of key genes. All microRNAs (boxed) begin development
in the off state and rise at specific times, and their targets are repressed accordingly,
leading to falling protein levels. Not all factors are shown.
4. microRNA SWITCHES
The hallmark of the developmental timing mechanism is the sequen-
tial action of microRNAs, which are 21-25 nucleotides long, the shortest
functional RNAs known. These RNAs bind sequences in the 3
0
UTRs of
target mRNAs, slowing, reducing, or blocking the accumulation of the
encoded proteins (
Ambros, 2011
).
lin-4
encodes a microRNAwhich begins to accumulate from the mid-L1
and is constitutively expressed thereafter (
Feinbaum & Ambros, 1999; Lee,
Feinbaum, & Ambros, 1993
). The LIN-14 protein is normally present early
in the L1 and is downregulated as development proceeds (
Ruvkun &
Giusto, 1989
). Sequences complementary to the
lin-4
RNA are present
in the
lin-14
mRNA's 3
0
UTR, and these are missing in the
lin-14
dominant
alleles (
Wightman et al., 1991; Wightman, Ha, &Ruvkun, 1993
). Thus, the
loss of
lin-4
or the
lin-14
3
0
UTR sequences causes LIN-14 protein to
