Abstract. Although poly-(ADP ribose) polymerase 1 (PARP1) and PARylation of histones have been known for over 50 years and have been successfully targeted

During transcription, histone chaperones are essential for nucleosome disassembly and reassembly. Warner et al. provide evidence that the Spt6 N-terminal domain is essential for this process. The Spt6 NTD interacts directly with histones and is required for normal chromatin structure. Genetic evidence closely connects Spt6 with the histone chaperone FACT.

The authors discover a homeostatic process termed interstasis, in which an increased concentration of proteins within RNA–protein condensates induces the sequestration of their own mRNAs.

The genome is compacted in the nucleus through a hierarchical chromatin organization, ranging from chromosome territories to compartments, topologically associating domains (TADs), and individual nucl...

Abstract. The nucleosome remodeler Chd1 is required for the re-establishment of nucleosome positioning in the wake of transcription elongation by RNA Polym

The active site of RNA Polymerase II is highly conserved. Here the authors show that mutations can propagate effects across the enzyme and alter genetic behavior of distal residues, demonstrating plas...

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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

Letter to the Editor

We generated a genome-scale, genetic interaction network from the analysis of more than 4 million double mutants in the haploid human cell line, HAP1. The network maps ~90,000 genetic interactions, in...