In vivo, Argonaute-bound microRNAs exist predominantly in a reservoir of low molecular weight complexes not associated with mRNA Journal Article
| Authors: | La Rocca, G.; Olejniczak, S. H.; González, A. J.; Briskin, D.; Vidigal, J. A.; Spraggon, L.; DeMatteo, R. G.; Radler, M. R.; Lindsten, T.; Ventura, A.; Tuschl, T.; Leslie, C. S.; Thompson, C. B. |
| Article Title: | In vivo, Argonaute-bound microRNAs exist predominantly in a reservoir of low molecular weight complexes not associated with mRNA |
| Abstract: | 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/threo-nine-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. |
| Keywords: | protein kinase b; s6 kinase; adult; nonhuman; t cells; cell proliferation; t lymphocyte; animal cell; mouse; animal tissue; gene targeting; complex formation; microrna; protein assembly; protein stability; in vivo study; cell differentiation; phosphatidylinositol 3 kinase; messenger rna; mammalian target of rapamycin; gene repression; hematopoietic cell; argonaute protein; molecular weight; t lymphocyte activation; mtor; rac protein; rna induced silencing complex; intracellular signaling; argonaute; gw182; interleukin 3; priority journal; article; polyadenylic acid binding protein; non-transformed cell |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 112 |
| Issue: | 3 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2015-01-20 |
| Start Page: | 767 |
| End Page: | 772 |
| Language: | English |
| DOI: | 10.1073/pnas.1424217112 |
| PROVIDER: | scopus |
| PMCID: | PMC4311832 |
| PUBMED: | 25568082 |
| DOI/URL: | |
| Notes: | Export Date: 2 March 2015 -- Source: Scopus |
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