Metabolite sensing in eukaryotic <scp>mRNA</scp> biology

Clingman, Carina C.; Ryder, Seán

doi:10.1002/wrna.1167

Cited by 12 publications

(10 citation statements)

References 80 publications

(171 reference statements)

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“…Interestingly, male HFD and HFD-PF rats had similarly decreased VMH Bdnf expression compared with LFD males in spite of differences in their energy status, suggesting that dietary high-fat content, instead of increases in body fat or leptin, was associated with the decrease in Bdnf expression in male rats. Increasing evidence supports the idea that dietary fat components and their metabolites could directly regulate gene transcription/post-transcription and second-messenger systems [27]. Fat metabolic enzymes may affect mRNA stability or translation efficiency and fat metabolites can be sensed via a regulatory segment of mRNA to change mRNA activity or even regulate RNA editing [27].…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence supports the idea that dietary fat components and their metabolites could directly regulate gene transcription/post-transcription and second-messenger systems [27]. Fat metabolic enzymes may affect mRNA stability or translation efficiency and fat metabolites can be sensed via a regulatory segment of mRNA to change mRNA activity or even regulate RNA editing [27]. …”

Section: Discussionmentioning

confidence: 99%

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Effects of energy status and diet on Bdnf expression in the ventromedial hypothalamus of male and female rats

Liu

Zhu

Kalyani

et al. 2014

Physiology & Behavior

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Sex differences exist in the regulation of energy homeostasis in response to calorie scarcity or excess. Brain-derived neurotrophic factor (BDNF) is one of the anorexigenic neuropeptides regulating energy homeostasis. Expression of Bdnf mRNA in the ventromedial nucleus of the hypothalamus (VMH) is closely associated with energy and reproductive status. We hypothesized that Bdnf expression in the VMH was differentially regulated by altered energy balance in male and female rats. Using dietary intervention, including fasting-induced negative energy status and high-fat diet (HFD) feeding-induced positive energy status, along with low-fat diet (LFD) feeding and HFD pair-feeding (HFD-PF), effects of diets and changes in energy status on VMH Bdnf expression were compared between male and female rats. Fasted males but not females had lower VMH Bdnf expression than their fed counterparts following 24-hour fasting, suggesting that fasted males reduced Bdnf expression to drive hyperphagia and body weight gain. Male HFD obese and HFD-PF non-obese rats had similarly reduced expression of Bdnf compared with LFD males, indicating that dampened Bdnf expression was associated with feeding a diet high in fat instead of increased adiposity. Decreased BDNF signaling during HFD feeding would increase a drive to eat and may contribute to diet-induced obesity in males. In contrast, VMH Bdnf expression was stably maintained in females when energy homeostasis was disturbed. These results suggest sex-distinct regulation of central Bdnf expression by diet and energy status.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of energy status and diet on Bdnf expression in the ventromedial hypothalamus of male and female rats

Liu

Zhu

Kalyani

et al. 2014

Physiology & Behavior

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“…Genetic control of cellular metabolism often involves sensing of mRNA secondary structures by nutrients and metabolites or interactions with RBPs (Sudarsan et al 2003;Clingman and Ryder 2013). These mRNA structures are widespread in prokaryotes and also identified in handful of eukaryotes.…”

Section: Structural Rnasmentioning

confidence: 99%

“…In prokaryotes, these are referred to as RNA genetic switches which are typically located in noncoding regions of mRNAs (such as UTR regions) of many metabolic enzymes and can modulate gene expression. In eukaryotes, metabolic enzymes can interact with mRNAs to affect mRNA stability or translation efficiency (Clingman and Ryder 2013). We have identified base-paired mRNA elements in the coding region of P. falciparum metabolic enzymes, with most enrichment of duplex RNAs in the Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (PF3D7_1012400) and Adenosylhomocysteinase (SAHH) (PF3D7_0520900).…”

Section: Structural Rnasmentioning

confidence: 99%

The RNA Structurome in the Asexual Blood Stages of Malaria PathogenPlasmodium falciparum

Alvarez

Ospina

Dey

et al. 2020

Preprint

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RNA as an effector of biological functions often adopts secondary and tertiary structural folds. Plasmodium falciparum is a deadly human pathogen responsible for the devastating disease called malaria. In this study, we measured the differential accumulation of RNA secondary structures in coding and noncoding transcripts from the asexual developmental cycle in P. falciparum in human red blood cells. Our comprehensive analysis, combining high-throughput nuclease mapping of RNA structures by duplex RNA-seq, immunoaffinity purification and RNA analysis, collectively measured differentially base-paired RNA regions during the parasite development. Our mapping data not only aligned to a diverse pool of RNAs with known structures but also enabled us to identify new structural RNA regions in the malaria genome. On average, ~71% of the genes with secondary structures are found to be protein coding mRNAs. Mapping pattern of these base-paired RNAs corresponded to all portions of protein-coding mRNAs, including 5- UTR, CDS and 3- UTR. In addition to histone family genes which are known to form secondary structures in their mRNAs, transcripts from genes which are important for transcriptional and post-transcriptional control, such as unique plant-like transcription factor family, ApiAP2, DNA/RNA binding protein family, Alba, ribosomal proteins and eukaryotic initiation factors involved in translational control and the ones important for RBC invasion and cytoadherence also show strong accumulation of duplex RNA reads in various asexual stages. Intriguingly, our study determined a positive relationship between mRNA structural contents and translation efficiency in P. falciparum asexual blood stages, suggesting an essential role of RNA structural changes in malaria gene expression programs.

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“…Furthermore, riboswitches in prokaryotes may function both transcriptionally and translationally. In eukaryotes, on the other hand, metabolite sensing is often indirect via proteins that then bind RNA and appears to be restricted to post-transcriptional regulation [ 54 ].…”

Section: Application Scenariosmentioning

confidence: 99%

RNA folding with hard and soft constraints

Lorenz

Hofacker

Stadler

2016

Algorithms Mol Biol

102

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BackgroundA large class of RNA secondary structure prediction programs uses an elaborate energy model grounded in extensive thermodynamic measurements and exact dynamic programming algorithms. External experimental evidence can be in principle be incorporated by means of hard constraints that restrict the search space or by means of soft constraints that distort the energy model. In particular recent advances in coupling chemical and enzymatic probing with sequencing techniques but also comparative approaches provide an increasing amount of experimental data to be combined with secondary structure prediction.ResultsResponding to the increasing needs for a versatile and user-friendly inclusion of external evidence into diverse flavors of RNA secondary structure prediction tools we implemented a generic layer of constraint handling into the ViennaRNA Package. It makes explicit use of the conceptual separation of the “folding grammar” defining the search space and the actual energy evaluation, which allows constraints to be interleaved in a natural way between recursion steps and evaluation of the standard energy function.ConclusionsThe extension of the ViennaRNA Package provides a generic way to include diverse types of constraints into RNA folding algorithms. The computational overhead incurred is negligible in practice. A wide variety of application scenarios can be accommodated by the new framework, including the incorporation of structure probing data, non-standard base pairs and chemical modifications, as well as structure-dependent ligand binding.Electronic supplementary materialThe online version of this article (doi:10.1186/s13015-016-0070-z) contains supplementary material, which is available to authorized users.

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Metabolite sensing in eukaryotic mRNA biology

Cited by 12 publications

References 80 publications

Effects of energy status and diet on Bdnf expression in the ventromedial hypothalamus of male and female rats

Effects of energy status and diet on Bdnf expression in the ventromedial hypothalamus of male and female rats

The RNA Structurome in the Asexual Blood Stages of Malaria PathogenPlasmodium falciparum

RNA folding with hard and soft constraints

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