Stephen RoyleJun 16, 2025
Bruce Hamilton

Lab preprint now in PubMed:
Nonequivalence of Zfp423 premature termination codons in mice.

In which two overlapping indel variants that predict the same frameshift, stop codon, and potential reinitiation codon have very different outcomes.
https://doi.org/10.1101/2025.05.30.656936

Jun 15, 2025 at 5:39pmIceCubesApp
Show threadMichael EmermanJun 15, 2025
@bahome Interesting work. In viral genomes, termination codons within ORFs are nonequivalent due to different frequency of readthrough, rather than reinitiation. e.g. https://www.science.org/doi/10.1126/sciadv.ads7933
Show threadBruce HamiltonJun 15, 2025
@memerman Thanks! And yes, I don’t think I could dream up a mechanism that a virus has not already exploited. For our case, the protein size shift is consistent with reinitiation but not read-through. Based on reporter assays, the difference between fs alleles seems to be mediated by RNA secondary structure.
Show threadBruce HamiltonJun 15, 2025
@memerman and Harmit’s work in particular is always interesting. Our students invited as a keynote for the Genetics program retreat a couple years ago and he was awesome.
Show threadMichael EmermanJun 15, 2025
@bahome  
One of my retirement plans is to attend Harmit's group meeting when the virus projects are discussed.