We use PEtracer to reconstruct high-resolution lineage histories for >1.4 million cells from E7.5 to E10.0 during mouse development, providing a quantitative view of fate bias, restriction timing, and...

Mammalian biology unfolds over time, within tissues and organs opaque to our eyes and instruments. We applied DNA Typewriter, a sequential molecular recorder, to record the cell lineage of a mouse ove...

The genomic regions regulating gene expression are often themselves transcribed into a variety of noncoding RNAs (ncRNAs). However, the regulatory roles of this noncoding transcription remain largely ...

DNA replication generates sister chromatids with identical sequence, yet its mechanism is fundamentally asymmetric: Chromatids inherit strands of opposite orientation, whereas forks synthesize new str...

Artificial intelligence enables the design of RNA pseudoknots

RNA design has been hindered by the limited accuracy of three-dimensional (3D) structure prediction. In this study, we show that intricate RNA structures can be generated with current deep learning to...

The generation of functional viral genomes has urgent biosafety and biosecurity implications

Many important biological functions arise not from single genes but from complex interactions encoded by entire genomes. We report the first generative design of complete bacteriophage genomes using g...

Preferential insertion into the late-replicating inactive X explains L1 accumulation in this chromosome

X-chromosome inactivation (XCI) enables gene dosage compensation in XX eutherians. Long interspersed element-1 (LINE-1 or L1) retrotransposons are unusually abundant on the human X chromosome and are ...

Phase plates can, in principle, overcome the poor image contrast in cryo–electron microscopy (cryo-EM) and the resulting limits on the structural reconstruction of small proteins. However, previous de...

Podcast Episode · Science Magazine Podcast · May 21 · 41m

A better understanding of battles between bacteria and viruses could inspire new medicines

Synonymous codon usage controls global gene expression in both prokaryotic and eukaryotic species. Nonoptimal codons are known to induce mRNA decay; however, the underlying molecular mechanism remains...

How intrinsically disordered regions (IDRs) influence chromatin binding and nuclear organization of transcription factors (TFs) remains unclear. We employed proximity-assisted photoactivation (PAPA), ...

A structure-based approach identifies bacteriophage proteins that block bacterial immunity

Immune systems in animals, plants, and bacteria often rely on intracellular nucleotide signaling, which viruses can block by sequestering or degrading these signals. We identified structural and bioph...

Kinetic proofreading is a class of error-correcting mechanisms in biology that expend energy to avoid mistakes during replication, transcription, and translation. Proofreading is typically assumed to ...

Fragments of aberrant cytoplasmic mRNA pair with nuclear RNAs to augment transcription

Transcriptional adaptation (TA) is a genetic robustness mechanism through which mutant messenger RNA (mRNA) decay induces sequence-dependent up-regulation of so-called adapting genes. How cytoplasmica...

Some RNA molecules can create their own mirror images, suggesting similar molecules could have sparked life

Eukaryotic gene expression is orchestrated by RNA polymerases (RNAPI, II, and III) and associated factors, yet their real-time dynamics remain obscure. Using single-molecule tracking in living yeast, ...

Site-specific insertion of gene-sized DNA fragments remains an unmet need in the genome editing field. IS110-family serine recombinases have recently been shown to mediate programmable DNA recombinati...

Biological function is fundamentally determined by nucleic acid and protein sequence. Beyond encoding genetic information, nucleic acids also display complex physicochemical parameters that shape stru...

Enigmatic ‘vaults’ can be engineered to eavesdrop on RNA, aiding cancer studies and more

Understanding how cells make decisions over time requires the ability to link past molecular states to future phenotypic outcomes. We present TimeVault, a genetically encoded system that records and s...

Recent breakthroughs in protein structure prediction have opened new avenues for genome-wide drug discovery, yet existing virtual screening methods remain computationally prohibitive. We present DrugC...

Mammalian SWI/SNF chromatin remodeling complexes modulate DNA accessibility and gene expression; however, their genomic targeting mechanisms remain incompletely understood. Here, we identify SWIFT (SW...

Biological systems are inherently complex and heterogeneous. Deciphering this complexity increasingly relies on high-throughput single-cell omics methods and tools that efficiently probe the cellular ...

Single-cell sequencing methods uncover natural and induced variation between cells. Many functional genomic methods, however, require multiple steps that cannot yet be scaled to high throughput, inclu...

During eukaryotic transcription, Pol II must overcome nucleosome obstacles and, because of DNA’s helical structure, must also rotate relative to DNA, generating torsional stress. However, there is lim...

A protein that cuts double-stranded DNA contributes to chromosome scrambling in human cancer cells

Genome instability, including chromothripsis, is a hallmark of cancer. Cancer cells frequently contain micronuclei—small, nucleus-like structures formed by chromosome missegregation—that are susceptib...

Roger Highfield, Science Director, describes the first real stride toward writing human genomes from scratch.

The synthesis of human genomes and other gigabase-scale genomes will require new strategies. Here, we realized key steps in our pipeline for building synthetic human chromosomes. We established: (i) t...

Extrusive and cohesive cohesin cooperate to repair double-strand breaks in DNA

Cohesin folds genomes into chromatin loops, the roles of which are under debate. We found that double-strand breaks (DSBs) induce de novo formation of chromatin loops in human cells, with the loop bas...

Accurate repair of DNA double-strand breaks (DSBs) is essential for genome stability, and defective repair underlies diseases such as cancer. Homologous recombination uses an intact homologous sequenc...

Cryogenic electron tomography of condensed chromatin enables multiscale analysis of its structure