A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism

Pradas-Juni, Marta; Hansmeier, Nils Rouven; Link, Jenny; Schmidt, Elena; Larsen, Bjørk Ditlev; Klemm, Paul; Meola, Nicola; Topel, Hande; Loureiro, Rute; Dhaouadi, Ines; Kiefer, Christoph; Schwarzer, Robin; Khani, Sajjad; Oliverio, Matteo; Awazawa, Motoharu; Frommolt, Peter; Heeren, Joerg; Scheja, Ludger; Heine, Markus; Dieterich, Christoph; Büning, Hildegard; Yang, Ling; Cao, Haiming; Jesus, Dario F. De; Kulkarni, Rohit; Zevnik, Branko; Tröder, Simon E.; Knippschild, Uwe; Edwards, Peter A.; Lee, Richard G.; Yamamoto, Masayuki; Ulitsky, Igor; Fernández-Rebollo, Eduardo; Vallim, Thomas Q. de Aguiar; Kornfeld, Jan-Wilhelm

doi:10.1038/s41467-020-14323-y

Cited by 36 publications

(25 citation statements)

References 75 publications

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“…Noncoding RNAs, in particular microRNAs (miRNAs) (~18-24 nucleotides) and long noncoding RNAs (lncRNAs) (> 200 nucleotides), can be affected by changes in nutrient availability [119][120][121]. MicroRNAs (miRNAs) (18-24 nucleotides) can also regulate mitochondrial function, cellular quiescence, and maturation through epigenetic mechanisms involving posttranscriptional regulation of mRNA [25,122].…”

Section: Noncoding Rnasmentioning

confidence: 99%

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Garbern

Lee

2021

Stem Cell Res Ther

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Current methods to differentiate cardiomyocytes from human pluripotent stem cells (PSCs) inadequately recapitulate complete development and result in PSC-derived cardiomyocytes (PSC-CMs) with an immature or fetal-like phenotype. Embryonic and fetal development are highly dynamic periods during which the developing embryo or fetus is exposed to changing nutrient, oxygen, and hormone levels until birth. It is becoming increasingly apparent that these metabolic changes initiate developmental processes to mature cardiomyocytes. Mitochondria are central to these changes, responding to these metabolic changes and transitioning from small, fragmented mitochondria to large organelles capable of producing enough ATP to support the contractile function of the heart. These changes in mitochondria may not simply be a response to cardiomyocyte maturation; the metabolic signals that occur throughout development may actually be central to the maturation process in cardiomyocytes. Here, we review methods to enhance maturation of PSC-CMs and highlight evidence from development indicating the key roles that mitochondria play during cardiomyocyte maturation. We evaluate metabolic transitions that occur during development and how these affect molecular nutrient sensors, discuss how regulation of nutrient sensing pathways affect mitochondrial dynamics and function, and explore how changes in mitochondrial function can affect metabolite production, the cell cycle, and epigenetics to influence maturation of cardiomyocytes.

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Section: Noncoding Rnasmentioning

confidence: 99%

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Garbern

Lee

2021

Stem Cell Res Ther

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“…For example, the lncRNA Xist, which is crucial for X-chromosome dosage compensation in female cells in eutherian mammals, introduces a repressed chromatin state marked by extensive histone-H3 K27me3 across one of the Xchromosomes, leading to X-inactivation and Barr body formation [10,11], while the oncogenic lncRNA HOTAIR promotes cancer metastasis in part by silencing HOXA genes by promoting K27-trimethylation and K4-demethylation of histone-H3 [12]. In the liver, lncRNAs have been linked to liver fibrosis through their effects on glucose metabolism (LincIRS2) [13] and hepatic stellate cell regulation (H19, Meg3, HOTTIP) [14][15][16]. However, the biological functions and mechanisms of action of the vast majority of lncRNAs expressed in liver and other tissues are unknown.…”

Section: /14/21mentioning

confidence: 99%

Global analysis of expression, maturation and subcellular localization of mouse liver transcriptome identifies novel sex-biased and TCPOBOP-responsive long non-coding RNAs

Goldfarb

Waxman

2021

Preprint

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While nuclear transcription and RNA processing and localization are well established for protein coding genes (PCGs), these processes are poorly understood for lncRNAs. Here, we characterize global patterns of transcript expression, maturation and localization for mouse liver RNA, including more than 15,000 lncRNAs. PolyA-selected liver RNA was isolated and sequenced from four subcellular fractions (chromatin, nucleoplasm, total nucleus, and cytoplasm), and from the chromatin-bound fraction without polyA selection. Transcript processing, determined from normalized intronic to exonic sequence read density ratios, progressively increased for PCG transcripts in going from the chromatin-bound fraction to the nucleoplasm and then on to the cytoplasm. Transcript maturation was similar for lncRNAs in the chromatin fraction, but was significantly lower in the nucleoplasm and cytoplasm. LncRNAs were 11-fold more likely to be significantly enriched in the nucleus than cytoplasm, and 100-fold more likely to be significantly chromatin-bound than nucleoplasmic. Sequencing chromatin-bound RNA greatly increased the sensitivity for detecting lowly expressed lncRNAs and enabled us to discover and localize hundreds of novel regulated liver lncRNAs, including lncRNAs showing sex-biased expression or responsiveness to a xenobiotic agonist ligand of constitutive androstane receptor (Nr1i3). Integration of our findings with prior studies and lncRNA annotations identified candidate regulatory lncRNAs for a variety of hepatic functions based on gene co-localization within topologically associating domains or transcription divergent or antisense to PCGs associated with pathways linked to hepatic physiology and diseases.

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“…Notably, mRNA‐lncRNA axis also plays a vital role in regulating glucose metabolism. LincIRS2 was repressed in diet‐induced obese mouse, which was controlled by increased transcription factor MafG (MAFG) signaling, and then control the hepatic glucose metabolism in obesity syndromes 66 . This provides a method for future studies to find the factors involved in regulating lncRNA expression that plays an important role in the prevention of obesity syndrome.…”

Section: Regulation Of Lncrnas In Obesity Syndromes‐related Metabolismmentioning

confidence: 99%

The role of long noncoding RNA in lipid, cholesterol, and glucose metabolism and treatment of obesity syndrome

Guo

Liu

et al. 2020

Medicinal Research Reviews

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Obesity syndromes, characterized by abnormal lipid, cholesterol, and glucose metabolism, are detrimental to human health and cause many diseases, including obesity and type II diabetes. Increasing evidence has shown that long noncoding RNA (lncRNA), transcripts longer than 200 nucleotides that are not translated into proteins, play an important role in regulating abnormal metabolism in obesity syndromes. For the first time, we systematically summarize how lncRNA is involved in complex obesity metabolic syndromes, including the regulation of lipid, cholesterol, and glucose metabolism. Moreover, we discuss lncRNA involvement in food intake that mediates obesity syndromes. Furthermore, this review might shed new light on a lncRNA‐based strategy for the prevention and treatment of obesity syndromes. Recent investigations support that lncRNA is a novel molecular target of obesity syndromes and should be emphasized. Namely, lncRNA plays a crucial role in the development of obesity syndrome process. Various lncRNAs are involved in the process of lipid, cholesterol, and glucose metabolism by regulating gene transcription, signaling pathway, and epigenetic modification of metabolism‐related genes, proteins, and enzymes. Food intake could also induce abnormal expression of lncRNA associated with obesity syndrome, especially high‐fat diet. Notably, some nanomolecules and natural extracts may target lncRNAs, associated with obesity syndrome, as a potential treatment for obesity syndromes.

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A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism

Cited by 36 publications

References 75 publications

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Global analysis of expression, maturation and subcellular localization of mouse liver transcriptome identifies novel sex-biased and TCPOBOP-responsive long non-coding RNAs

The role of long noncoding RNA in lipid, cholesterol, and glucose metabolism and treatment of obesity syndrome

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