Transcriptional initiation and termination decisions drive messenger RNA (mRNA) isoform diversity but the relationship between them remains poorly understood. By systematically profiling joint usage o...

Protein ubiquitination regulates cell biology through diverse avenues, from quality control-linked protein degradation to signaling functions such as modulating protein-protein interactions and enzyme...

Phylogenetic mining and protein language models uncover improved PiggyBac transposase sequences.

Structural RNAs exhibit a vast array of recurrent short three-dimensional (3D) elements found in loop regions involving non-Watson–Crick interactions that help arrange canonical double helices into tertiary structures. Here we present CaCoFold-R3D, a probabilistic grammar that predicts these RNA 3D motifs (also termed modules) jointly with RNA secondary structure over a sequence or alignment. CaCoFold-R3D uses evolutionary information present in an RNA alignment to reliably identify canonical helices (including pseudoknots) by covariation. Here we further introduce the R3D grammars, which also exploit helix covariation that constrains the positioning of the mostly noncovarying RNA 3D motifs. Our method runs predictions over an almost-exhaustive list of over 50 known RNA motifs (‘everything’). Motifs can appear in any nonhelical loop region (including three-way, four-way and higher junctions) (‘everywhere’). All structural motifs as well as the canonical helices are arranged into one single structure predicted by one single joint probabilistic grammar (‘all-at-once’). Our results demonstrate that CaCoFold-R3D is a valid alternative for predicting the all-residue interactions present in a RNA 3D structure. CaCoFold-R3D is fast and easily customizable for novel motif discovery and shows promising value both as a strong input for deep learning approaches to all-atom structure prediction as well as toward guiding RNA design as drug targets for therapeutic small molecules.

Post-transcriptional gene regulation through m6A deposition is dysregulated in many diseases and is catalyzed by a multi-protein writer complex. This Unsolved Mystery investigates why the writer compl...

Programmable DNA integration using CRISPR-associated transposons (CASTs) offers powerful capabilities for genome engineering. The single effector Cas12k CAST examples evolved from a fixed guide TnpB n...

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 ...

imageimagePaternal environmental exposures have been linked with modulation of phenotype and disease risk in offspring via largely unclear mechanisms. This study employs in vitro fertilization and sin...

Wei et al. show that the primary function of m6A on the nuclear long noncoding RNA Xist, a master regulator of X inactivation, is to promote RNA degradation. Xist turnover is mediated by the nuclear e...

Circular RNAs (circRNAs) are enriched in synapses and implicated in cognitive processes, and recent studies have shown that circRNAs can encode micropeptides, which suggests that there may be novel sy...

N6-methyladenosine (m6A) is a critical regulator of mRNA processing and function, impacting nearly every step of the mRNA lifecycle. Changes in m6A status have been implicated in many different types ...

Genes are often activated by enhancers located at large genomic distances, and the importance of this positioning is poorly understood. By relocating promoter-reporter constructs into thousands of alt...

DNA methylation loss at transposable elements (TEs) can affect neighboring genes and be epigenetically inherited in plants, yet the determinants and significance of this additional system of inheritan...

Why are some species widespread while others are found only in small, isolated areas? This study shows that species with narrow ranges, and thus higher extinction risk, are often island-restricted, poor dispersers, and have evolved relatively recently.

This study introduces SDR-seq, a droplet-based single-cell DNA–RNA sequencing platform, enabling the study of gene expression profiles linked to both noncoding and coding variants.

N-glycans on glycoRNAs prevent innate immune sensing of endogenous small RNAs, and the natural mechanism they use demonstrates how glycoRNAs exist on the cell surface and in the endosomal network with...

Mutations within promoters and coding sequences are both involved in adaptation, but their relative contributions remain to be compared directly. Using the fungal enzyme cytosine deaminase, we examine...