The application of real‐time NMR experiments to the study of RNA folding, as reviewed in this article, is relatively new. For many RNA folding events, current investigations suggest that the time scales are in the second to minute regime. In addition, the initial investigations suggest that different folding rates are observed for one structural transition may be due to the hierarchical folding units of RNA. Many of the experiments developed in the field of NMR of protein folding cannot directly be transferred to RNA: hydrogen exchange experiments outside the spectrometer cannot be applied since the intrinsic exchange rates are too fast in RNA, relaxation dispersion experiments on the other require faster structural transitions than those observed in RNA. On the other hand, information derived from time‐resolved NMR experiments, namely the acquisition of native chemical shifts, can be readily interpreted in light of formation of a single long‐range hydrogen bonding interaction. Together with mutational data that can readily be obtained for RNA and new ligation technologies that enhance site resolution even further, time‐resolved NMR may become a powerful tool to decipher RNA folding. Such understanding will be of importance to understand the functions of coding and non‐coding RNAs in cells. © 2007 Wiley Periodicals, Inc. Biopolymers 86: 360–383, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

MicroRNAs (miRNAs) interact with 3′-untranslated regions of messenger RNAs to restrict expression of most protein-coding genes during normal development and cancer. RNA-binding proteins (RBPs) can control the biogenesis, stability and activity of miRNAs. Here we identify RBM38 in a genetic screen for RBPs whose expression controls miRNA access to target mRNAs. RBM38 is induced by p53 and its ability to modulate miRNA-mediated repression is required for proper p53 function. In contrast, RBM38 shows lower propensity to block the action of the p53-controlled miR-34a on SIRT1. Target selectivity is determined by the interaction of RBM38 with uridine-rich regions near miRNA target sequences. Furthermore, in large cohorts of human breast cancer, reduced RBM38 expression by promoter hypermethylation correlates with wild-type p53 status. Thus, our results indicate a novel layer of p53 gene regulation, which is required for its tumour suppressive function.

The metal ion-induced folding of the Diels-Alder ribozyme into a catalytically active form with a complex RNA pseudoknot has been characterized by static and time-resolved NMR spectroscopy. The conformations of two sequences from the Diels-Alder ribozyme family, A27 WT and G27 MUT, were studied in the absence and presence of metal ions and of ligand. The single nucleotide mutant G27 MUT in the absence of metal ions displayed conformational heterogeneity which greatly influences its folding trajectory. Time-resolved NMR experiments were applied using a sample-mixing technique to rapidly add Ca(2+) ions to induce folding in situ. The folding rates observed for the G27 MUT ribozyme differed by 3 orders of magnitude from the A27 WT folding rates determined previously by FRET experiments. A model based on the characterization of the free and metal-bound forms of the ribozymes is proposed to account for the difference in the folding rates of the two ribozymes. Evidence is provided that the reactivity is modulated due to local dynamics around the catalytic pocket for the G27 MUT ribozyme.

Background Numerous diets, apps and websites help guide and monitor dietary behaviour with the goal of losing weight, yet dieting success is highly dependent on personal preferences and circumstances. To enable a more quantitative approach to dieting, we developed an integrated platform that allows tracking of life-style information alongside molecular biofeedback measurements (lactate and insulin). Methods To facilitate weight loss, participants (≥18 years) omitted one main meal from the usual three-meal routine. Daily caloric intake was restricted to ~1200KCal with one optional snack ≤250KCal. A mobile health platform ( personalhealth.warwick.ac.uk ) was developed and used to maintain diaries of food intake, weight, urine collection and volume. A survey was conducted to understand participants’ willingness to collect samples, motivation for taking part in the study and reasons for dropout. Results Meal skipping resulted in weight loss after a 24 h period in contrast to 3-meal control days regardless of the meal that was skipped, breakfast, lunch or dinner ( p < 0.001). Common reasons for engagement were interest in losing weight and personal metabolic profile. Total insulin and lactate values varied significantly between healthy and obese individuals at p = 0.01 and 0.05 respectively. Conclusion In a proof of concept study with a meal-skipping diet, we show that insulin and lactate values in urine correlate with weight loss, making these molecules potential candidates for quantitative feedback on food intake behaviour to people dieting. Electronic supplementary material The online version of this article (10.1186/s40608-019-0237-5) contains supplementary material, which is available to authorized users.

Angiotensin Converting Enzyme (ACE) expression and activity is associated with obesity. ACE is a circulating factor that predicts sustained weight loss over a time frame of months. Here, we evaluate whether ACE might also be an early marker (over a 24-hour period) for weight loss. 32 participants (78% females; BMI 28.47 ± 4.87kg/m2) followed a 1200KCal diet with an optional daily (<250KCal) snack and were asked to use an in-house generated health platform to provide recordings of food intake, physical activity and urine collection time and volume. Following a day of dieting, ACE levels in urine negatively correlated with weight loss (p = 0.015). This reduction in ACE levels was significantly more robust in individuals with a BMI > 25 (p = 0.0025). This study demonstrated that ACE levels correlate with BMI and weight loss as early as after 1 day of dieting, and thus ACE could be a potential early "biofeedback" marker for weight loss and diet efficiency.Recording of eating patterns through questionnaires with or without computer assistance has been recognized as an effective step in managing obesity [12][13][14]. However, regardless of interface, reporting of too low or too high caloric/energy intake as compared to true intake is a well-documented problem [11,15,16]. This unconscious bias is associated with under-realization and in some scenarios even over-estimation of foods eaten [11,17]. Even if food tracking was entirely accurate, it might not provide sufficient motivation for people to lose weight [11,18]. Thus, an approach to weight loss is needed that is more directly linked to the desired outcome, weight loss, itself [11,19]. A quantitative and science-based biomarker of weight loss is needed to provide immediate/short-term biological feedback loop during dieting.Urinary metabolic markers for cardiovascular disease, blood pressure and adiposity have been identified [20,21]. Several metabolomics studies involving untargeted proton (1H) nuclear magnetic resonance spectroscopy (NMR) and ion exchange chromatography (IEC) with human and mice urine samples have identified metabolites associated with BMI and adiposity [20,22]. Quantitative biomarkers have not been considered for providing early (especially over a 24-hour period) feedback to an individual undergoing a weight loss intervention.The extent of reduction in ACE has been shown through blood profiling for protein and steroid hormones to be an important predictor for sustained weight loss on long time scales [23]. The participants who kept their weight off after one year also had decreased ACE concentrations at the end of an eight-week low caloric diet. ACE is a zinc metallopeptidase involved in the conversion of Angiotensin (Ang) I to Angiotensin II [23][24][25][26]. Ang I is obtained by cleavage of Angiotensinogen (AGT) with the help of renin. Ang II is a well-known for its role in increased blood pressure and retention of salt and water [24,27,28]. In addition, animal models have shown that increased adipose specific angiotensin (AGT) expression and sec...