Biology Reference
In-Depth Information
A
WT
V1
let-7 (
-
)
lin-41 (
-
)
V1
V1
L1
L2
L3
L4
Adult
B
let-7 (
-
)
WT
Egg laying defective (egl)
Protruding vulva (pVul)
Ruptured vulva (rup)
Figure 1.3
C. elegans let-7 mutant phenotypes. (A) The lineage division patterns of
wild-type (WT) V1 hypodermal seam cells are shown for the larval (L1-L4) and adult
stages. In WT worms, V1 cells divide at each molt, with one cell differentiating (gray)
and the other continuing to divide at the next stage (white), until the cells terminally
differentiate at adulthood (gray). Worms with loss-of-function mutations in let-7 (let-7
(
)) have retarded heterochronic phenotypes where V1 cells can undergo one or more
additional divisions after L4, sometimes failing to execute the adult differentiated fate
(striped). The opposite phenotype, precocious, is expressed by worms with loss of
lin-41 (lin-41(
)), where the V1 cells terminate dividing and take on the differentiated
adult fate at the L3 to L4 molt. (B) Pictures of adult worms at 200
magnification; the
anterior is to the left and the vulva is on the ventral side. WT adult worms form eggs,
which they lay through their vulva, a narrow opening that is smoothly in line with the
ventral side of the worm. Worms with mutations in let-7 display a variety of easily
identifiable vulval phenotypes. Egg laying defective (egl) is characterized by a bloated,
egg-filled worm. Protruding vulva (pVul) is defined by a protrusion due to abnormal
development of the vulva. Ruptured vulva (rup) occurs during the L3 to L4 molt, when
the worm innards burst through the weak unstructured vulva, resulting in lethality.
(
Fig. 1.4
;
Kanamoto
et al.
, 2006; Maller-Schulman
et al.
, 2008; Pasquinelli
et al.
, 2000
). The discovery of let-7 across species fueled the search for other
such RNA genes, and soon many small RNAs were identified in worms,
flies, human cell lines, mice, and plants through cloning methods (
Lagos-
Quintana
et al.
, 2001, 2002; Lau
et al.
, 2001; Lee and Ambros, 2001;
Reinhart
et al.
, 2002
). A signature of these
21nt RNAs is that they are
processed from
65nt stem-loop precursors, and this feature distinguishes
the class of miRNAs from other tiny ncRNAs (
Ambros
et al.
, 2003
).
While there is one
let-7
gene in
C. elegans
, multiple let-7 genes exist in
most vertebrates. The human genome includes three let-7 genes that
