Semidilute solutions of persistence length, mononucleosomal DNA (160 ± 5 base pairs, , = 1.06 x 105) with and without added salt have been studied by small-angle X-ray scattering (SAXS). The DNA concentration ranged from 30 to 182 mg/mL. The scattering intensity of salt-free solutions displays a broad maximum at scattering vector qm, indicative of solution structure caused by the electrostatic and excludedvolume interactions between charged DNA fragments. The peak vanishes when enough salt is added that the screened coulomb potential becomes shorter range than the interparticle distance. qm scales with the DNA concentrations as C1/2. This accords with scaling theory and similar predictions and agrees with SAXS and small-angle neutron scattering results obtained by others on semidilute solutions of semiflexible synthetic polyelectrolytes. When account is taken of the expanded effective DNA diameter in no-salt or low-salt solutions, these solutions have number densities p above the limit (vde¡(L2/4)p > 4.48 predicted by Onsager to lead to a transition to an anisotropic, liquid crystalline phase. The peak spacing under these conditions is consistent with hexagonally aligned arrays. However, we observe no evidence of anisotropy. This may be confirmation of the suggestion by Stroobants et al. (1986) that twisting forces between charged rods (for which the crossed orientation has a lower energy than the parallel) raise the concentration required for the transition.

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A large number of signalling pathways converge on p53 to induce different cellular stress responses that aim to promote cell cycle arrest and repair or, if the damage is too severe, to induce irreversible senescence or apoptosis. The differentiation of p53 activity towards specific cellular outcomes is tightly regulated via a hierarchical order of post-translational modifications and regulated protein-protein interactions. The mechanisms governing these processes provide a model for how cells optimize the genetic information for maximal diversity. The p53 mRNA also plays a role in this process and this review aims to illustrate how protein and RNA interactions throughout the p53 mRNA in response to different signalling pathways control RNA stability, translation efficiency or alternative initiation of translation. We also describe how a p53 mRNA platform shows riboswitch-like features and controls the rate of p53 synthesis, protein stability and modifications of the nascent p53 protein. A single cancer-derived synonymous mutation disrupts the folding of this platform and prevents p53 activation following DNA damage. The role of the p53 mRNA as a target for signalling pathways illustrates how mRNA sequences have co-evolved with the function of the encoded protein and sheds new light on the information hidden within mRNAs.

We have applied scaling theory to published data on the osmotic pressure II of solutions of the polyelectrolytes sodium poly(styrenesu1fonate) (NaF'SS) and poly(styrenesu1fonic acid) (HPSS) without added salt. The data cover 4 decades of polymer concentration C; molecular weights M range from 20 to 1060 K. Three different concentration regimes are observed. In the low concentration regime, Jl depends on molecular weight. In the semidilute regime, scaling predictions are accurately obeyed: II is independent of M, and the slope of II vs C is 1.125. In this regime, the dependence of II on C also agrees well with predictions of the Poisson-Boltzmann cylindrical cell model theory, though only if the linear charge spacing used in the calculations is somewhat less than the structural value. A dramatic increase in osmotic pressure is observed in the concentrated regime. The slope of II vs C is close to 2.25, the value predicted from scaling theory for semidilute neutral polymer solutions. This suggests that polyelectrolytes may adopt an expanded random-coil chain conformation in highly concentrated solutions without added salt.

A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as putative eRNA-target pairs. The interactive web servers, TANRIC (the Atlas of Noncoding RNAs in Cancer) and cBioPortal, were used to explore the RNA levels and clinical data from the Cancer Genome Atlas (TCGA) project. Requiring that key eRNAs should show significant associations with overall survival (Kaplan–Meier log-rank test, p < 0.05) and the predicted target (correlation coefficient r > 0.4, p < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was AP001056.1 with ICOSLG encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with AP001056.1 (r > 0.4, p < 0.001), with the “immune system process” being the most significantly enriched biological process (adjusted p < 0.001). Our results suggest that AP001056.1 is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome.