miR-7 is recruited to the High Molecular Weight 1 RNA-induced silencing complex in CD8+ T cells upon activation and suppresses IL-2 signaling

Matilda Toivakka, Katrina Gordon, Sujai Kumar, Jose Roberto Bermudez Barrientos, Cei Abreu-Goodger, Rose Zamoyska*, Amy H. Buck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Increasing evidence suggests mammalian Argonaute (Ago) proteins partition into distinct complexes within cells, but there is still little biochemical or functional understanding of the miRNAs differentially associated with these complexes. In naïve T cells, Ago2 is found almost exclusively in low molecular weight (LMW) complexes which are associated with miRNAs but not their target mRNAs. Upon T-cell activation, a proportion of these Ago2 complexes move into a newly formed high molecular weight (HMW) RNA-induced silencing complex (RISC), which is characterized by the presence of the GW182 protein that mediates translational repression. Here, we demonstrate distinct partitioning of miRNAs and isomiRs in LMW versus HMW RISCs upon antigen-mediated activation of CD8 + T cells. We identify miR-7 as highly enriched in HMW RISC and demonstrate that miR-7 inhibition leads to increased production of IL-2 and up-regulation of the IL-2 receptor, the transferrin receptor, CD71 and the amino acid transporter, CD98. Our data support a model where recruitment of miR-7 to HMW RISC restrains IL-2 signaling and the metabolic processes regulated by IL-2.

Original languageEnglish
Pages (from-to)26-36
JournalRNA
Volume30
Early online date25 Oct 2023
DOIs
Publication statusE-pub ahead of print - 25 Oct 2023

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