Biology Reference
In-Depth Information
A
GW182
Argonaute
Endonucleolytic
cleavage
m
7
G
AAAAA
B
GW182
Deadenylation
Argonaute
CCR1-CAF1-NOT
complex
m
7
G
AAAAA
C
Repression of
translation initiation
GW182
Argonaute
m
7
G
AAAAA
D
Repression after
translation initiation
GW182
Argonaute
m
7
G
AAAAA
Figure 1.2
Mechanisms of miRNA target regulation. (A) When miRNAs bind to
target sites with a high level of complementarity, it triggers endonucleolytic cleavage of
the mRNA by Argonaute (Ago). (B) Ago interacts with GW182 proteins, which bind
to the CCR1-CAF1-NOT complex to trigger deadenylation of bound target mRNAs.
(C, D) Through unclear mechanisms, the Ago-GW182 complex represses translation
(C) by inhibiting translation initiation and (D) by blocking protein accumulation after
translation has initiated.
posttranscriptional mechanism acting at a stage after translational initiation
(
Olsen and Ambros, 1999; Wightman
et al.
, 1993
). Subsequent work
showed that mRNA levels for the
lin-14
,
lin-28
, and
lin-41
target
mRNAs are downregulated in response to miRNA regulation, and there
is also a shift on polysomes indicative of inhibition of translation initiation
(
Bagga
et al.
, 2005; Ding and Groszhans, 2009
). It remains to be determined
if target mRNA degradation is a cause or consequence of halted translation.
Argonaute interacts with GW182 proteins (AIN-1 and AIN-2 in
C. elegans
),
which recruit factors capable of interfering with translation or promoting
deadenylation of the target mRNA (
Tritschler
et al.
, 2010
). Thus, depend-
ing on the cell type or conditions, different factors may be available to
regulate miRNA targets through diverse mechanisms, ultimately resulting
in diminished protein production.
