Biology Reference
In-Depth Information
Figure 1.4
Examples of let-7 target site interactions. Illustrated here is the imperfect
pairing between let-7 and 3
0
UTR sequences in lin-41 (also called Trim71 in mammals)
genes in C. elegans, M. musculus, and H. sapiens.
Figure 1.5
Homologs of let-7 in worms and humans. The let-7 family of genes is
defined by the conserved seed sequence (nt 2-7). In C. elegans, let-7 has six nonidentical
“sister” miRNAs. The human genome contains three genes that produce mature
miRNAs identical to the worm let-7 (let-a-1, let-7a-2, let-a-3), two copies of let-7f
and eight other miRNAs that share the let-7 seed sequence.
produce mature RNAs of identical sequence (let-7a-1, let-a-2, let-7a-3) as
well as nine others that differ by one or more nucleotides (
Fig. 1.5
). Since
the seed sequence, nucleotides 2-7, of the miRNA plays a key role in target
recognition, miRNAs with identical seeds are often considered part of a
family (
Lim
et al.
, 2005
). MiRNAs within the same family potentially
regulate common targets, thus explaining why mutation of one member
sometimes results in no discernible phenotypes (
Miska
et al.
, 2007
).
In
C. elegans
,
let-7
has six “sister” genes that share 5
0
end sequences
(
Fig. 1.5
). Nonetheless, mutation of
let-7
alone is sufficient to cause devel-
opmental abnormalities and lethality in
C. elegans
(
Fig. 1.3
;
Reinhart
et al.
,
2000
). Thus, members of a miRNA family do not necessarily compensate
for each other. In mammals, some of the let-7 family members exhibit
