AI Article Synopsis
- MicroRNAs (miRNAs) are crucial noncoding RNAs that help regulate human mRNA protein production after transcription, but their relationship with Argonaute (Ago) proteins is more complex than previously thought.
- There is a significant excess of miRNAs compared to Ago proteins in HeLa cells, suggesting that not all miRNAs are directly bound by Agos, leading to the possibility of miRNA-mRNA interactions without Agos.
- While all human Agos can repress these miRNA-mRNA interactions, only Ago2 has the ability to cleave small interfering RNA-mRNA duplexes, indicating a distinct role of Agos in regulating gene expression.
Article Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate protein output from the majority of human mRNAs. In contrast to the consensus view that all miRNAs are associated with Argonaute (Ago) proteins, we determine that miRNAs are expressed in a 13-fold excess relative to Agos in HeLa cells and that miRNAs are bound to mRNAs in a sevenfold excess relative to Agos, implying the existence of miRNA-mRNA duplexes not stoichiometrically bound by Agos. We show that all four human Agos can repress miRNA-mRNA duplexes, but only Ago2 can cleave small interfering RNA-mRNA duplexes in vitro. We visualize direct Ago binding to miRNA-mRNA duplexes in live cells using fluorescence lifetime imaging microscopy. In contrast to the consensus view that Agos bind miRNA duplexes, these data demonstrate that Agos can bind and repress miRNA-mRNA duplexes and support a model of catalytic Ago function in translational repression.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479394 | PMC |
| http://dx.doi.org/10.1261/rna.035675.112 | DOI Listing |
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