2 research outputs found
Mating can initiate stable RNA silencing that overcomes epigenetic recovery
Partial funding for Open Access provided by the UMD Libraries' Open Access Publishing FundStable epigenetic changes appear uncommon, suggesting that changes typically dissipate or
are repaired. Changes that stably alter gene expression across generations presumably
require particular conditions that are currently unknown. Here we report that a minimal
combination of cis-regulatory sequences can support permanent RNA silencing of a singlecopy
transgene and its derivatives in C. elegans simply upon mating. Mating disrupts competing
RNA-based mechanisms to initiate silencing that can last for >300 generations. This
stable silencing requires components of the small RNA pathway and can silence homologous
sequences in trans. While animals do not recover from mating-induced silencing, they often
recover from and become resistant to trans silencing. Recovery is also observed in most cases
when double-stranded RNA is used to silence the same coding sequence in different regulatory
contexts that drive germline expression. Therefore, we propose that regulatory features
can evolve to oppose permanent and potentially maladaptive responses to transient
change.https://doi.org/10.1038/s41467-021-24053-
nucGEMs probe the biophysical properties of the nucleoplasm
Abstract The cell interior is highly crowded and far from thermodynamic equilibrium. This environment can dramatically impact molecular motion and assembly, and therefore influence subcellular organization and biochemical reaction rates. These effects depend strongly on length-scale, with the least information available at the important mesoscale (10-100 nanometers), which corresponds to the size of crucial regulatory molecules such as RNA polymerase II. It has been challenging to study the mesoscale physical properties of the nucleoplasm because previous methods were labor-intensive and perturbative. Here, we report nuclear Genetically Encoded Multimeric nanoparticles (nucGEMs). Introduction of a single gene leads to continuous production and assembly of protein-based bright fluorescent nanoparticles of 40 nm diameter. We implemented nucGEMs in budding and fission yeast and in mammalian cell lines. We found differences in particle motility between the nucleus and the cytosol at the mesoscale, that mitotic chromosome condensation ejects nucGEMs from the nucleus, and that nucGEMs are excluded from heterochromatin and the nucleolus. nucGEMs enable hundreds of nuclear rheology experiments per hour, and allow evolutionary comparison of the physical properties of the cytosol and nucleoplasm