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Thrilled to share our latest research on 3′UTR-derived RNAs, now published in BMC Biology! https://doi.org/10.1186/s12915-024-02032-7
Here’s what we found:
Thrilled to share our latest research on 3′UTR-derived RNAs, now published in BMC Biology! https://doi.org/10.1186/s12915-024-02032-7
Here’s what we found:
Comments
CAGE profiling often reveals signals (~10-15%) in 3′UTRs — regions far from usual transcription start sites (TSS). This phenomenon is reproducible but poorly understood.
It has been suggested that 3′UTR CAGE signals arise from post-transcriptional cleavage followed by capping of exposed 5′ ends. These processes might lead to independent, functional 3′UTR-derived RNAs.
By analysing our data alongside #ENCODE & #FANTOM datasets, we provide direct evidence that these 3′UTR-derived RNAs are capped, reproducible, conserved across mammals, and detectable via long-read sequencing.
By integrating AGO2-eiCLIP, eCLIP, and CAGE-seq, we found their origins linked to RNA-binding proteins, specifically AGO2 and UPF1. These sites are often rich in G-motifs capable of forming G-Quadruplexes.
Our analysis shows that AGO2 binds upstream of 3′UTR-derived RNA start sites—independent of miRNA binding. Interestingly, G4 motifs influence the binding positions of both AGO2 and UPF1, shaping the capping sites.
We also found that cytoplasmic capping can occur subsequent to AGO2/siRNA-mediated cleavage, by analysing FANTOM5 CAGE from siRNA-treated samples. Our findings demonstrate that capping can readily follow cytoplasmic cleavage, and is not exclusive to transcriptional initiation.