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specific expression patterns and have distinct targets, indicating that they
may play different roles in diverse biological pathways (
Boyerinas
et al.
,
2010; Chiang
et al.
, 2010
).
3. The Role of let-7 in C. elegans Development
3.1. Biogenesis of let-7
Consistent with its role in promoting later larval cell fates, mature let-7
miRNA starts to accumulate midway through the third larval stage of
development (
Fig. 1.6
;
Reinhart
et al.
, 2000; Van Wynsberghe
et al.
,
2011
). The
let-7
gene expresses three let-7 primary transcripts, two
unspliced variants with differing transcriptional start sites and one SL1
trans
-spliced isoform (
Bracht
et al.
, 2004
). The transcripts are capped and
polyadenylated via a conserved polyA signal located
670nt downstream of
the mature let-7 sequence. Surprisingly, expression of the let-7 primary
transcripts initiates at the end of the first larval stage and oscillates during
each subsequent stage (
Fig. 1.6
;
Van Wynsberghe
et al.
, 2011
). This expres-
sion pattern is regulated at the transcriptional level, as indicated by reporter
genes containing the let-7 promoter fused to GFP (
Esquela-Kerscher
et al.
,
2005; Johnson
et al.
, 2003; Martinez
et al.
, 2008; Van Wynsberghe
et al.
,
2011
). These reporter studies also show that let-7 appears to be transcribed
in most somatic tissues, consistent with the broad expression pattern of let-7
in differentiated cell types across animal species.
AAAAA
AAAAA
Stages of
development
L1
L2
L3
L4
Adult
mature let-7
pre-let-7
pri-let-7
Figure 1.6
Expression of let-7 throughout C. elegans development. Graphical depiction
of the accumulation of primary (pri-let-7), precursor (pre-let-7), and mature let-7 RNAs
during the larval (L1-L4) and adult stages of worm development based on data from
Van
Wynsberghe et al. (2011)
. Worm pictures were captured at 100
magnification.
