Jordy F. Botello

cell.comDeep learning of functional perturbations from condensate morphologyA deep learning method quantitatively decodes nucleolar, nuclear speckle, and viral condensate morphology to reveal underlying biochemical states. Applying this framework reveals a previously unrecogn...

Some molecular machines, like ribosomes, can persist for long periods of time in cells. Could molecular aging of ribosomes shape how proteins are made? In our new preprint we track ribosomes as they age in cells and uncover unexpected effects on translation (1/10) www.biorxiv.org/content/10.6...

Jordy F. Botello reposted

Anita Donlic

@anitadonlic.bsky.social

5 June

Thrilled to see our Deep-Phase paper now online in @cellcellpress.bsky.social! 🎉 The final version expands Deep-Phase across labeling modalities, adds dual-condensate imaging to dissect pathway specificity, and shows greater robustness to batch effects than classical image-analysis methods.

This work reflects the effort of many amazing collaborators: Lifei Jiang, Peter Metzger, Troy Comi, Aya Abu-Alfa, @qiweiyu.bsky.social, Margaret Ebert, Minkyu Lee, Lenny Wiesner, Maya Butani, Claire Weaver, Andrej Košmrlj, Ileana Cristea….. (9/10)

and Cliff @brangwynnelab.bsky.social for all the support and guidance through this journey! (10/10)

Does ribosome molecular aging occur in vivo? Using our strategy in C. elegans, we tracked ribosomes that persisted ≥8 days. These long-lived ribosomes showed reduced association with translating pools, linking ribosome molecular aging to organismal aging. (7/10)

Take home: Ribosomes undergo molecular aging in living cells. As ribosomes age, translation efficiency shifts, elongation defects increase at basic sequences, and ribosome collisions become more frequent. This suggests ribosome aging directly shapes translation dynamics. (8/10)

Not all ribosomes age equally. Profiling rRNA modifications reveals that collisions driven by aged ribosomes are enriched for ribosomes lacking the pseudouridine Ψ18S-210, demonstrating to a vulnerable ribosome subpopulation. (5/10)

Are aging ribosomes sufficient to drive these translation changes? Using a HaloPROTAC strategy, we selectively degraded newly made ribosomes, enriching the pool of older ones. This alone recapitulates the translation defects seen in aged ribosomes! (6/10)

Using our strategy, we performed molecular age-selective Ribo-seq to compare aged ribosomes with the steady-state pool. Result: ribosome molecular aging shapes the translation efficiency of specific transcripts classes! (3/10)

Why do aged ribosomes translate some mRNAs less efficiently? Older ribosomes pause more during elongation. Pausing sites are enriched for basic amino acids (K/R), suggesting molecular aging makes ribosomes more prone to stalling at polybasic sequences. (4/10)