Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

Over the past 5 to 7 million years, humans and chimpanzees have diverged in brain size, structural complexity, and cognitive abilities despite high conservation of protein-coding genes. Notably, the e...

Nature Reviews Genetics, Published online: 18 November 2025; doi:10.1038/s41576-025-00919-xIn this Journal Club, Nozomu Yachie recalls a 1999 paper by Pellegrini, Marcotte and colleagues that demonstrated how functional information, such as protein--protein interactions, could be revealed through patterns of genetic diversity across species.

Wang et al. find that cell membrane stress upon viral infection induces expression and stabilization of host sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B), which, in turn, degrades cGAMP to s...

Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although signaling circuits and gene regulatory networks that regulate pluripotent stem cell diffe...

Dendritic nanotubes extend brain connectivity beyond synapses

Launching in April 2025, the Max Planck Postdoc Program features structured application calls and a comprehensive support system for researchers.

Background Neuropsychiatric disorders are highly complex conditions and the risk of developing a disorder has been tied to hundreds of genomic variants that alter the expression and/or RNA isoforms made by risk genes. However, how these genes contribute to disease risk and onset through altered expression and RNA splicing is not well understood. Results Combining our new bioinformatic pipeline IsoLamp with nanopore long-read amplicon sequencing, we deeply profile the RNA isoform repertoire of 31 high-confidence neuropsychiatric disorder risk genes in Human brain. We show most risk genes are more complex than previously reported, identifying 363 novel isoforms and 28 novel exons, including isoforms which alter protein domains, and genes such as ATG13 and GATAD2A where most expression was from previously undiscovered isoforms. The greatest isoform diversity is detected in the schizophrenia risk gene ITIH4. Mass spectrometry of brain protein isolates confirms translation of a novel exon skipping event in ITIH4, suggesting a new regulatory mechanism for this gene in the brain. Conclusions Our results emphasize the widespread presence of previously undetected RNA and protein isoforms in the human brain and provide an effective approach to address this knowledge gap. Uncovering the isoform repertoire of candidate neuropsychiatric risk genes will underpin future analyses of the functional impact these isoforms have on neuropsychiatric disorders, enabling the translation of genomic findings into a pathophysiological understanding of disease.

Intercellular nanotubular networks mediate material exchange, but their existence in neurons remains to be explored in detail. We identified long, thin dendritic filopodia forming direct dendrite–dend...

Summary Amphisomes are hybrid organelles that result from fusion of late endosomes with autophagosomes. Here, we report that amphisomes containing BDNF/TrkB and capable of signaling are formed at pres...

Neuromesodermal progenitors (NMPs) produce the spinal cord and musculoskeleton in the elongating anterior-posterior axis. In vivo, NMPs possess dual potency, coinciding with regions coexpressing SOX2 ...

Multiplexed assays of variant effect (MAVEs) are highly scalable experimental approaches used to generate functional data for genetic variants. In this Review, McEwen et al. discuss the advances in MA...