David Sanders, Ph.D., Assistant Professor in the Center for Alzheimer’s and Neurodegenerative Diseases and Molecular Biology at UT Southwestern Medical Center, has been awarded $2.4 million over five ...

A combination of whole-genome NanoSeq with deep whole-exome and targeted NanoSeq is used to accurately characterize mutation rates and genes under positive selection in sperm cells.

In terms of its relative frequency, lysine is a common amino acid in the human proteome. However, by bioinformatics we find hundreds of proteins that contain long and evolutionarily conserved stretches completely devoid of lysine residues. These so-called lysine deserts show a high prevalence in intrinsically disordered proteins with known or predicted functions within the ubiquitin-proteasome system (UPS), including many E3 ubiquitin-protein ligases and UBL domain proteasome substrate shuttles, such as BAG6, RAD23A, UBQLN1 and UBQLN2. We show that introduction of lysine residues into the deserts leads to a striking increase in ubiquitylation of some of these proteins. In case of BAG6, we show that ubiquitylation is catalyzed by the E3 RNF126, while RAD23A is ubiquitylated by E6AP. Despite the elevated ubiquitylation, mutant RAD23A appears stable, but displays a partial loss of function phenotype in fission yeast. In case of UBQLN1 and BAG6, introducing lysine leads to a reduced abundance due to proteasomal degradation of the proteins. For UBQLN1 we show that arginine residues within the lysine depleted region are critical for its ability to form cytosolic speckles/inclusions. We propose that selective pressure to avoid lysine residues may be a common evolutionary mechanism to prevent unwarranted ubiquitylation and/or perhaps other lysine post-translational modifications. This may be particularly relevant for UPS components as they closely and frequently encounter the ubiquitylation machinery and are thus more susceptible to nonspecific ubiquitylation.

Intrinsically disordered regions (IDRs) have emerged as crucial regulators of protein function, allowing proteins to sense and respond to their environment. Creb binding protein (CBP) and EP300 (p300)...

Cryo–electron tomography visualizes stress granules in situ, revealing their spatial interplay with translation machinery.

Biomolecular condensates are complex droplets comprising diverse molecules that interact by various mechanisms. Condensation is often driven by short-range attraction, but net charges can also mediate...

Using a unique longitudinal sampling approach, Louw et al. demonstrate how a cheese-associated Penicillium population has adapted in an artisan cheese production facility in Vermont, USA. Adaptation i...

Freire-Delgado and Brunet discover a new mode of cell motility in choanoflagellates, the closest relatives of animals. Under mild confinement, choanoflagellate move over surfaces without cell deformat...

Simon Baeckens and Colin Donihue review case studies of rapid evolutionary change in response to extreme climate events and sketch a framework for future studies in the rapidly changing climate of the...

During organogenesis, precise pre-mRNA splicing is essential to assemble tissue architecture. Many developmentally essential exons bear weak 5'splice sites (5'SS) yet are spliced with high precision, ...