Custom DNA constructs have never been more common or important in the life sciences. Many researchers therefore devote substantial time and effort to molecular cloning, aided by abundant computer-aide...

Kaur et al. demonstrate reduced histone acetylation as a key mechanism underpinning Wolbachia’s paternal-effect embryonic lethality trait in Drosophila melanogaster. Recapitulation of this trait by in...

NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Information for the NIH Extramural Community During the Lapse of Federal Government Funding NOT-OD-26-004. NIH

The Department of Molecular Biology (MOLB) and the School of Computing (SoC) at the University of Wyoming seeks candidates for a tenure-track position at the rank of Assistant Professor starting in th...

NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Stephen I. Katz Early Stage Investigator Research Project Grant (R01 Clinical Trial Not Allowed) PAR-25-322. OD

As a proof-of-concept for analyte-responsive polymers (ARPs) for biosensing, this study investigates how ligand binding changes the temperature-dependent dynamics and self-assembly of an elastin-like polymer (ELP) fused with a peptide recognition element for the small globular protein domain SH3. Using isothermal titration calorimetry, we characterized the apparent binding thermodynamics when one binding partner is fused with an ELP. Circular dichroism, dynamic light scattering, and temperature-dependent UV–vis spectroscopy were used to examine how ligand binding influences ARP conformational dynamics and phase behavior. SH3 binding was associated with an increase in transition temperature that reproduced in a complex medium and was consistent with predictions from a published model for ELP fusions. Addition of SH3 destabilized ARP assemblies, demonstrating that an ARP response can be specifically triggered by ligand binding. This work advances our understanding of how ligand binding and phase behavior are interdependent in systems involving intrinsically disordered proteins and their assemblies.

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

Sethuraman Panchanathan, a Trump appointee who has led the agency since 2020, leaves amid mass firings and grant terminations