By Mike Gilman, serial entrepreneur and veteran biotech executive, as part of the From The Trenches feature of LifeSciVC My thesis advisor, Mike Chamberlin, passed away last week. I owe much of who I ...

AlphaFold - A practical guide

More than 2,700 human mRNA 3′UTRs have hundreds of highly conserved (HC) nucleotides, but their biological roles are unclear. Here, we show that mRNAs with HC 3′UTRs mostly encode proteins with long intrinsically disordered regions (IDRs), including MYC, UTX, and JMJD3. These proteins are only fully active when translated from mRNA templates that include their 3′UTRs, raising the possibility of functional interactions between 3′UTRs and IDRs. Rather than affecting protein abundance or localization, we find that HC 3′UTRs control transcriptional or histone demethylase activity through co-translationally determined protein oligomerization states that are kinetically stable. 3′UTR-dependent changes in protein folding require mRNA-IDR interactions, suggesting that mRNAs act as IDR chaperones. These mRNAs are multivalent, a biophysical RNA feature that enables their translation in network-like condensates, which provide favorable folding environments for proteins with long IDRs. These data indicate that the coding sequence is insufficient for the biogenesis of biologically active conformations of IDR-containing proteins and that RNA can catalyze protein folding. ### Competing Interest Statement The authors have declared no competing interest. Pershing Square Foundation, https://ror.org/04tce9s05 G. Harold & Leila Y. Mathers Foundation National Institutes of Health, DP1GM123454, R35GM144046 Memorial Sloan Kettering Cancer Center, https://ror.org/02yrq0923, P30 CA008748

Integrator (INT) prevents the escape of immature RNAPII to ensure full-length mRNA production. INT deficiency causes defects in RNAPII maturation that lead to premature termination, accumulation of immunogenic dsRNA, and activation of the integrated stress response (ISR) observed in patient cells.

If we stay on this administration’s course, future life-saving medicines may never be invented

Nature Reviews Molecular Cell Biology, Published online: 07 April 2025; doi:10.1038/s41580-025-00846-zThis study shows that zotatifin selectively inhibits the translation of prostate cancer oncogene transcripts by restructuring their 5′ untranslated regions. In mice, this agent reversed treatment resistance, which led to improved survival.

The major backer of the lenacapavir roll-out is assuring nervous researchers that they will keep their part of funding promises. It’s a good economic investment, says the Fund’s Peter Sands, into a ga...

View Ann Carol Palmenberg, Ph.D's obituary, find service dates, and sign the guestbook.

University of Michigan's professor A. Oveta Fuller spent her career battling against the myths surrounding HIV and COVID. Two of her mentees reflect on her legacy.

The War on Science What’s happening? What can we do about it? An interactive teach-in for biomedical researchers Please share, modify, and repurpose this template presentation (with credit). Good luck...