In vivo, Argonaute-bound microRNAs exist predominantly in a reservoir of low
molecular weight complexes not associated with mRNA
#MMPMID25568082
La Rocca G
; Olejniczak SH
; González AJ
; Briskin D
; Vidigal JA
; Spraggon L
; DeMatteo RG
; Radler MR
; Lindsten T
; Ventura A
; Tuschl T
; Leslie CS
; Thompson CB
Proc Natl Acad Sci U S A
2015[Jan]; 112
(3
): 767-72
PMID25568082
show ga
MicroRNAs repress mRNA translation by guiding Argonaute proteins to partially
complementary binding sites, primarily within the 3' untranslated region (UTR) of
target mRNAs. In cell lines, Argonaute-bound microRNAs exist mainly in high
molecular weight RNA-induced silencing complexes (HMW-RISC) associated with
target mRNA. Here we demonstrate that most adult tissues contain reservoirs of
microRNAs in low molecular weight RISC (LMW-RISC) not bound to mRNA, suggesting
that these microRNAs are not actively engaged in target repression. Consistent
with this observation, the majority of individual microRNAs in primary T cells
were enriched in LMW-RISC. During T-cell activation, signal transduction through
the phosphoinositide-3 kinase-RAC-alpha serine/threonine-protein
kinase-mechanistic target of rapamycin pathway increased the assembly of
microRNAs into HMW-RISC, enhanced expression of the glycine-tryptophan protein of
182 kDa, an essential component of HMW-RISC, and improved the ability of
microRNAs to repress partially complementary reporters, even when expression of
targeting microRNAs did not increase. Overall, data presented here demonstrate
that microRNA-mediated target repression in nontransformed cells depends not only
on abundance of specific microRNAs, but also on regulation of RISC assembly by
intracellular signaling.
free
free
free
