The C-terminal domain (CTD) of RNA polymerase II acts as a regulatory platform during the transcription cycle. Here, the authors use a simple tail CTD and reveal how repeating sequence patterns and ch...

Lea et al. find that some kinases form highly concentrated condensates that enrich ATP through electrostatic potential and significantly increase rates of trans-autophosphorylation. Condensates that e...

Highly conserved mRNA 3′ UTRs act as co-translational chaperones for intrinsically disordered regions (IDRs), preventing inter-domain misfolding and enabling biogenesis of fully active proteins.

Intrinsically disordered protein regions (IDPs) are found across the tree of life and characterized by the lack of a stable 3D fold, encoding function through a vast ensemble of conformations. This pl...

A deep learning method quantitatively decodes nucleolar, nuclear speckle, and viral condensate morphology to reveal underlying biochemical states. Applying this framework reveals a previously unrecogn...

Honest evaluations of biological foundation models. We rank and review AI for protein folding, genomics, single-cell analysis, and more.

This Review discusses how long noncoding RNAs (lncRNAs) control transcription activation by RNA polymerase II, including how they are produced at active enhancers or chromatin-domain boundaries and ac...

CRISPR perturbation of ∼4 million gene pairs in human HAP1 cells maps ∼89,000 genetic interactions, revealing a hierarchical network that links genes to complexes, pathways, and cellular processes and...

Regulation of RNA polymerase II (Pol II) transcription is closely associated with cell proliferation. However, it remains unclear how the Pol II transcription program is rewired in cancer to promote u...

Langstein-Skora, Schmid, Huth et al. propose that intrinsically disordered region functionality can be driven by the interplay between linear binding motifs and contextual chemical characteristics suc...

The deep learning model STARLING can generate accurate ensembles of intrinsically disordered regions of proteins using only protein sequence as input.

CU Anschutz welcomes Alice Soragni to launch a Functional Personalized Medicine Initiative using rapid tumor organoid testing to guide treatment decisions.

Interactions between long RNA molecules play essential roles in shaping gene regulation. Here, the authors show that low-complexity repeats drive stable contacts between RNAs and present RIME, a deep ...

Intrinsically disordered arginine-glycine-rich (RG/RGG) regions are highly abundant in the eukaryotic proteome. Proteins containing these motifs participate in fundamental cellular processes, including nuclear import, transcriptional regulation, biomolecular condensate formation, and apoptosis. Mutations or dysfunction of RG/RGG proteins have been implicated in neurodegenerative diseases and cancer. Although some RG/RGG proteins have been shown to drive condensate formation, localize to membrane-less organelles, interact with nuclear import receptors, or undergo arginine methylation, these properties are not shared uniformly across the proteome. The considerable diversity in RG/RGG motif length and amino acid composition raises the question of which sequence features determine their functional behaviour. To address this, we conducted a systematic bioinformatics and experimental analysis, combining synthetic and natural peptides with studies on the RNA-binding protein FUS as a model system. Our results reveal that the sequence composition of RG/RGG motifs is a key determinant of their capacity for RNA-mediated condensate formation, stress granule recruitment, and transportin-1–mediated chaperoning and nuclear import. These findings provide new insight into the sequence grammar of disordered RG/RGG regions and how it encodes the multifunctionality of these proteins in cellular regulation. ### Competing Interest Statement The authors have declared no competing interest. FWF Austrian Science Fund, https://ror.org/013tf3c58, 10.55776/COE14, 10.55776/P28854, 10.55776/I3792, 10.55776/DOC130 Austrian Research Promotion Agency, https://ror.org/028jc0449, 912192

Those who have “drifted” but still value the teachings that shaped us need to start being the body of Christ we wish to see.

Structural steps along the assembly of proteasome storage granules—membraneless organelles that form in response to metabolic shifts in yeast—are visualized inside cells by cryo-electron tomography. Inactive 26S proteasomes oligomerize into trimers, which assemble into paracrystalline arrays that serve as reservoirs of fully assembled proteasomes under conditions of low energy, ready for reactivation when glucose is restored.

RNA binding proteins (RBPs) play essential roles in post-transcriptional gene regulation by interacting with a wide range of RNA targets. In addition to regulating RNA processing via individual RBP-RNA interactions, there is a growing appreciation of the regulatory impact of protein-associated RNA-R …

Plants continuously experience temperature fluctuations that shape their physiology, development, and survival. Yet, how plants sense and adapt to elevated temperatures at the molecular level remains ...

Under stress, cells adapt their gene expression programs through changes in transcription and translation. It is unclear how cells determine which mRNAs are translated or repressed. Zedan et al. show that the timing of mRNA production alone determines the selectivity of translation, thereby coupling the processes of transcription and translation.

Transposable elements (TEs) – long considered ‘junk DNA’ – challenge the binary of threat and therapeutic opportunity in cancer. Their reactivation is not a singular event but a convergence of evoluti...

TDP-43 is an RNA binding protein implicated in neurodegenerative disease. TDP-43 binds to GU dinucleotide repeats, which are highly abundant sequences in human RNA. Here we show TDP- 43 has one of the...