The RNA-binding proteins DND1 and NANOS3 are essential for primordial germ cell survival. Their co-immunoprecipitation and overlapping loss-of-function phenotypes suggest joint function, yet how they ...

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.

UPF1 depletion inhibits nonsense-mediated mRNA decay (NMD) and stabilizes direct target transcripts within hours. Boehm et al. use conditional protein degradation and advanced transcriptomics to map t...

Vučićević et al. describe TESLA-seq, which combines pooled CRISPR activation with targeted single-cell RNA-seq to map enhancer-gene connections at high sensitivity. TESLA-seq was applied across a geno...

The cellular composition that defines the tumor ecosystem plays a crucial role in determining the responsiveness of tumors to immune checkpoint inhibitors (ICi) and pharmacological blockade of BRAF (B...

Cell-fate commitment in metazoan development relies on precise gene regulatory programs. This study presents a comprehensive single-cell atlas of gene expression (scRNA-seq), nascent transcription (sc...

SPIDR, a massively multiplexed method that simultaneously maps dozens of RNA-binding proteins to their RNA targets at single-nucleotide resolution, uncovers new RNA-protein interactions and provides c...

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

Wastewater-based epidemiology has already proven to be a powerful tool to monitor the spread of a number of diseases. This Perspective discusses the integration with machine learning, highlighting its...

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Die Helmholtz-Gemeinschaft bündelt ihre Aktivitäten in der Präventionsforschung und hat dafür die „Helmholtz Health Prevention Task Force“ ins Leben gerufen. In einem jetzt veröffentlichten Strategiep...

Complex RNA–protein networks play a pivotal role in the formation of many types of biomolecular condensates. How intrinsic RNA features contribute to condensate formation however remains unclear. Here...

The CCR4-NOT complex is a major regulator of eukaryotic messenger RNA (mRNA) stability. Slow decoding during translation promotes association of CCR4-NOT with ribosomes, accelerating mRNA degradation....

Zhou et al. discovered a specific role of adenosine modifications in the coding region of mRNAs. These chemical alterations slow down the movement of the ribosome during translation and trigger degrad...

imageimageTranscriptome-wide measurement of subcellular mRNA dynamics in mouse ES cells reveals that nuclear retention is the rate-limiting step in the life-cycle of most mRNAs and provides a resource for understanding spatiotemporal gene ...

Already Confirmed Speakers:Kirk Brown                        Alnylam Pharmaceuticals, USA