An exciting study driven by the close collaboration of first authors @erinduffyphd.bsky.social and @inespatop.bsky.social. And thanks to our other colleagues for making this such a comprehensive study. (11/11)

This work reveals RNA stability as a "hidden layer" of gene regulation that: 1) Operates independently of transcription 2) Works locally in neuronal processes 3) Is disrupted in neurodevelopmental disorders 4) Expands our view of activity-dependent plasticity (10/11)

Importantly, HuD-bound mRNAs are enriched for autism spectrum disorder (ASD) risk genes, and ASD variants can alter RNA stability regulation, implicating this pathway in neurodevelopmental disorders. (9/11)

How does activity change HuD function? Not by changing HuD levels, but by reorganizing its protein partners. Microscopy and IP-MS support a model where activity recruits HuD into RNA granules, stabilizing HuD-bound mRNAs by protecting them from degradation. (8/11)

We found that activity-dependent gene expression is modulated in both soma and distal processes (dendrites and axons), suggesting neurons may coordinate RNA stability, transport, and translation to adjust protein levels locally. (7/11)

To gain some mechanistic insight, we used MPRAs, machine learning, RIP-seq and metabolic labeling and identified the RNA binding protein HuD as a key regulator of activity-dependent RNA stability. (6/11)

And we did some in vivo validation: We also see effects on RNA stability in vivo in response to novel environment exploration, meaning this isn’t just a phenomenon in primary neurons, it also occurs in a physiologically relevant learning paradigm in the intact brain. (5/11)

RNA stability changes weren’t just a side effect. For ~10% of activity-dependent transcripts, stability mattered more than transcription for determining RNA levels, challenging the transcription-centric view of gene regulation in this process. (4/11)

Of ~5,000 activity-regulated transcripts, two thirds showed changes in transcription, which was expected. Unexpectedly, ~1,000 genes were regulated by RNA stability.(3/11)

When neurons fire, they need to rapidly change which genes are expressed to support processes like long-term memory. Transcriptional responses are well studied, but what about other steps in the RNA life cycle? (2/11)

I was inspired and made one last night! So good.

I'm late to this! That's the real deal! Go make a 1919 ASAP. :)