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Repeat RNA sequences self-associate to form condensates. Simulations of a coarse-grained single-interaction site model for (CAG)n (n = 30 and 31) show that the salt-dependent free energy gap, ΔGS, between the ground (perfect hairpin) and the excited state (slipped hairpin (SH) with one CAG overhang) of the monomer for (n even) is the primary factor that determines the rates and yield of self-assembly. For odd n, the free energy (GS) of the ground state, which is an SH, is used to predict the self-association kinetics. As the monovalent salt concentration, CS, increases, ΔGS and GS increase, which decreases the rates of dimer formation. In contrast, ΔGS for shuffled sequences, with the same length and sequence composition as (CAG)31, is larger, which suppresses their propensities to aggregate. Although demonstrated explicitly for (CAG) polymers, the finding of inverse correlation between the free energy gap and RNA aggregation is general. 

Low-complexity nucleotide repeat sequences, which are implicated in several neurological disorders, undergo liquid–liquid phase separation (LLPS) provided the number of repeat units, n , exceeds a critical value. Here, we establish a link between the folding landscapes of the monomers of trinucleotide repeats and their propensity to self-associate. Simulations using a coarse-grained Self-Organized Polymer (SOP) model for (CAG) n repeats in monovalent salt solutions reproduce experimentally measured melting temperatures, which are available only for small n . By extending the simulations to large n , we show that the free-energy gap, ΔG S , between the ground state (GS) and slipped hairpin (SH) states is a predictor of aggregation propensity. The GS for even n is a perfect hairpin (PH), whereas it is a SH when n is odd. The value of ΔG S (zero for odd n ) is larger for even n than for odd n . As a result, the rate of dimer formation is slower in (CAG) 30 relative to (CAG) 31 , thus linking ΔG S to RNA–RNA association. The yield of the dimer decreases dramatically, compared to the wild type, in mutant sequences in which the population of the SH decreases substantially. Association between RNA chains is preceded by a transition to the SH even if the GS is a PH. The finding that the excitation spectrum—which depends on the exact sequence, n , and ionic conditions—is a predictor of self-association should also hold for other RNAs (mRNA for example) that undergo LLPS. 

RNA molecules cannot fold in the absence of counterions. Experiments are typically performed in the presence of monovalent and divalent cations. How to treat the impact of a solution containing a mixture of both ion types on RNA folding has remained a challenging problem for decades. By exploiting the large concentration difference between divalent and monovalent ions used in experiments, we develop a theory based on the reference interaction site model (RISM), which allows us to treat divalent cations explicitly while keeping the implicit screening effect due to monovalent ions. Our theory captures both the inner shell and outer shell coordination of divalent cations to phosphate groups, which we demonstrate is crucial for an accurate calculation of RNA folding thermodynamics. The RISM theory for ion–phosphate interactions when combined with simulations based on a transferable coarse-grained model allows us to predict accurately the folding of several RNA molecules in a mixture containing monovalent and divalent ions. The calculated folding free energies and ion-preferential coefficients for RNA molecules (pseudoknots, a fragment of the rRNA, and the aptamer domain of the adenine riboswitch) are in excellent agreement with experiments over a wide range of monovalent and divalent ion concentrations. Because the theory is general, it can be readily used to investigate ion and sequence effects on DNA properties. 

Abstract Meiosis in the budding yeast Saccharomyces cerevisiae is used to create haploid yeast spores from a diploid mother cell. During meiosis II, cytokinesis occurs by closure of the prospore membrane, a membrane that initiates at the spindle pole body and grows to surround each of the haploid meiotic products. Timely prospore membrane closure requires SPS1, which encodes an STE20 family GCKIII kinase. To identify genes that may activate SPS1, we utilized a histone phosphorylation defect of sps1 mutants to screen for genes with a similar phenotype and found that cdc15 shared this phenotype. CDC15 encodes a Hippo-like kinase that is part of the mitotic exit network. We find that Sps1 complexes with Cdc15, that Sps1 phosphorylation requires Cdc15, and that CDC15 is also required for timely prospore membrane closure. We also find that SPS1, like CDC15, is required for meiosis II spindle disassembly and sustained anaphase II release of Cdc14 in meiosis. However, the NDR-kinase complex encoded by DBF2/DBF20MOB1 which functions downstream of CDC15 in mitotic cells, does not appear to play a role in spindle disassembly, timely prospore membrane closure, or sustained anaphase II Cdc14 release. Taken together, our results suggest that the mitotic exit network is rewired for exit from meiosis II, such that SPS1 replaces the NDR-kinase complex downstream of CDC15. 

Massive black holes (BHs) at the centres of massive galaxies are ubiquitous. The population of BHs within dwarf galaxies, on the other hand, is evasive. Dwarf galaxies are thought to harbour BHs with proportionally small masses, including intermediate mass BHs, with masses 102<106M⊙. Identification of these systems has historically relied upon the detection of light emitted from accreting gaseous discs close to the BHs. Without this light, they are difficult to detect. Tidal disruption events (TDEs), the luminous flares produced when a star strays close to a BH and is shredded, are a direct way to probe massive BHs. The rise times of these flares theoretically correlate with the BH mass. Here we present AT2020neh, a fast rising TDE candidate, hosted by a dwarf galaxy. AT2020neh can be described by the tidal disruption of a main sequence star by a 104.7−105.9M⊙ BH. We find the observable rate of fast rising nuclear transients like AT2020neh to be rare, at ≲2×10−8 events Mpc−3 yr−1. Finding non-accreting BHs in dwarf galaxies is important to determine how prevalent BHs are within these galaxies, and constrain models of BH formation. AT2020neh-like events may provide a galaxy-independent method of measuring IMBH masses.