Huge thanks to co-authors & collaborators, especially Kunal Shah for his support & Tyson Sharp for trusting me to lead this project. I’m also grateful to @BBSRC for funding my PhD and this discovery-led research, & to reviewers & editors whose feedback strengthened the paper.

Together, we propose that LIMD1 helps sequence-defined interactions mature into productive repression, revealing an adaptor-governed layer shaping the effectiveness & breadth of miRNA networks. The paper contains much more, so please give it a read! science.org/doi/full/10.1126…

In lung cancer, where LIMD1 is often lost early, a LIMD1-sensitive target signature was elevated in tumours, inversely correlated with LIMD1 & linked to poorer survival, suggesting that loss of adaptor-mediated miRNA control may be clinically relevant.

Dependence on LIMD1 was greatest for targets with lower seed GC content & conservation, despite predicted formation of stable duplexes. Erosion of this network increased target expression, indicating broad disruption of post-transcriptional control.

The results: LIMD1 supported productive targeting in a dose-dependent manner. Despite increased AGO2–miRNA binding, LIMD1-deficient cells showed a ~60% contraction in captured interactions, with each complex engaging fewer target transcripts & sites.

With @bio_eclipse, we used AGO2 chimeric eCLIP to identify miRNA–mRNA pairs across LIMD1 expression states in human lung cells. Combined with molecular, omics & computational analyses, this gave us a global and locus-resolved view of miRNA targeting.

Previous work from our lab showed that LIMD1 bridges AGO2 and the silencing machinery through distinct interfaces. We asked how this adaptor shapes the efficiency, breadth & evolutionary reach of microRNA targeting.

The 2024 Nobel Prize recognised the discovery of microRNAs, which transformed our understanding of gene regulation. Yet, 30 years later, targeting rules remain incomplete: even advanced RNA-centric models explain only around half the variation in measured repression.

Very happy to share that our study "The AGO2 adaptor LIMD1 expands the functional and evolutionary reach of microRNA targeting" is now published in @ScienceAdvances ! 🧬🥳🧬 science.org/doi/full/10.1126… Here’s what we found 🧵

Hmm, I'm not sure this study presents evidence indicating much at all. For instance, RE confounding effect of tobacco vs cannabis smokers, I remain a bit confused what they actually report - In study limitations they state they found epigenetic disruptions that remained 1/2

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