Transcription from CpG island (CGI) promoters controls the expression of two-thirds of mammalian genes, yet despite their prevalence, it remains unknown whether CGI-specific co-activators with intrins...

Some transcription factors can organize into different structural states, from small nanoscale clusters to macrophases. Here authors show that NHA9 undergoes differential conformational expansion acro...

The structure and interaction networks of molecules within biomolecular condensates are poorly understood. Using cryo–electron tomography and molecular dynamics simulations, we elucidated the structur...

Analysis of the longest-lived mammal, the bowhead whale, reveals an improved ability to repair DNA breaks, mediated by high levels of cold-inducible RNA-binding protein.  &nbs...

Condensates composed of the disordered region of the mediator of RNA polymerase II transcription subunit 1 (MED1) are known to partition specific proteins, but whether this specificity arises from ord...

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

LA JOLLA—The Salk Institute will welcome plant biologist Lucia Strader as a new professor and holder of the Howard H. and Maryam R. Newman Chair in Plant Biology in October 2025. Strader is an interna...

Designed protein pockets recognize intrinsically disordered protein regions

Nature Communications - Chromatin heterogeneity in the cell nucleus modulates the size, mobility, and formation of biomolecular condensates; decreasing chromatin heterogeneity correlates with...

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