Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity

Santoleri, Dominic; Lim, Hee-Woong; Emmett, Matthew J.; Stoute, Julian; Gavin, Matthew; Sostre-Colón, Jaimarie; Uehara, Kahealani; Welles, Jaclyn E.; Liu, Kathy Fange; Lazar, Mitchell A.; Titchenell, Paul M.

doi:10.1016/j.isci.2022.104410

Cited by 3 publications

(3 citation statements)

References 68 publications

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“…In response to feeding and elevated systemic insulin levels, the liver rapidly shifts from a state of catabolism to anabolism. Our lab and others have focused on defining the global transcriptional response to nutrient intake ( 27 ). However, the acute changes in liver metabolites that occur with feeding are less defined.…”

Section: Resultsmentioning

confidence: 99%

“…HA-nSREBP1c CHIP-Seq revealed SREBP1c binding near the transcription start site (TSS) of Ppp1r3b ( 36 ) ( Supplemental Figure 5A ). Furthermore, global run-on sequencing (GRO-Seq) data were examined to explore active sites of enhancers ( 27 ). Interestingly, an enhancer RNA (eRNA) in proximity of the Ppp1r3b gene colocalized with Srebp1c binding ( Supplemental Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

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mTORC1 controls murine postprandial hepatic glycogen synthesis via Ppp1r3b

Uehara,

Lee,

Stefkovich

et al. 2024

Journal of Clinical Investigation

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In response to a meal, insulin drives hepatic glycogen synthesis to help regulate systemic glucose homeostasis. The mechanistic target of rapamycin complex 1 (mTORC1) is a well-established insulin target and contributes to the postprandial control of liver lipid metabolism, autophagy, and protein synthesis. However, its role in hepatic glucose metabolism is less understood. Here, we used metabolomics, isotope tracing, and mouse genetics to define a role for liver mTORC1 signaling in the control of postprandial glycolytic intermediates and glycogen deposition. We show that mTORC1 is required for glycogen synthase activity and glycogenesis. Mechanistically, hepatic mTORC1 activity promotes the feeding-dependent induction of Ppp1r3b , a gene encoding a phosphatase important for glycogen synthase activity whose polymorphisms are linked to human diabetes. Reexpression of Ppp1r3b in livers lacking mTORC1 signaling enhances glycogen synthase activity and restores postprandial glycogen content. mTORC1-dependent transcriptional control of Ppp1r3b is facilitated by FOXO1, a well characterized transcriptional regulator involved in the hepatic response to nutrient intake. Collectively, we identify a role for mTORC1 signaling in the transcriptional regulation of Ppp1r3b and the subsequent induction of postprandial hepatic glycogen synthesis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mTORC1 controls murine postprandial hepatic glycogen synthesis via Ppp1r3b

Uehara,

Lee,

Stefkovich

et al. 2024

Journal of Clinical Investigation

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“…Several recent studies have indicated that ncRNAs are crucial in carcinogenesis by controlling the expression of cancer-associated genes [ 31 , 39 , 40 , 41 ]. Mechanistically, lncRNAs govern gene expression primarily by functioning as transcription factors, controlling chromatin remodeling, or actively contributing to posttranscriptional regulation as ceRNAs [ 42 , 43 , 44 ]. MiRNAs, on the other hand, control gene expression at the posttranscriptional level via RNA interference and frequently attach to the 3′-untranslated region (3′UTR) of protein-coding mRNAs and to the (5′UTR) or coding sequence [ 45 , 46 , 47 , 48 ].…”

Section: Functional Roles and Mechanisms Of Action Of Ncrnasmentioning

confidence: 99%

Emerging Roles and Potential Applications of Non-Coding RNAs in Cervical Cancer

Parashar

Singh

Gupta

et al. 2022

Genes

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Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current therapeutic options are very limited. Therefore, understanding the mechanism of metastasis and discovering new therapeutic targets are crucial. New sequencing tools have given a full visualization of the human transcriptome’s composition. Non-coding RNAs (NcRNAs) perform various functions in transcriptional, translational, and post-translational processes through their interactions with proteins, RNA, and even DNA. It has been suggested that ncRNAs act as key regulators of a variety of biological processes, with their expression being tightly controlled under physiological settings. In recent years, and notably in the past decade, significant effort has been made to examine the role of ncRNAs in a variety of human diseases, including cancer. Therefore, shedding light on the functions of ncRNA will aid in our better understanding of CC. In this review, we summarize the emerging roles of ncRNAs in progression, metastasis, therapeutics, chemo-resistance, human papillomavirus (HPV) regulation, metabolic reprogramming, diagnosis, and as a prognostic biomarker of CC. We also discussed the role of ncRNA in the tumor microenvironment and tumor immunology, including cancer stem cells (CSCs) in CC. We also address contemporary technologies such as antisense oligonucleotides, CRISPR–Cas9, and exosomes, as well as their potential applications in targeting ncRNAs to manage CC.

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Long Noncoding RNAs in the Pathogenesis of Insulin Resistance

Yang

Lyu

Xiang

et al. 2022

IJMS

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Insulin resistance (IR), designated as the blunted response of insulin target tissues to physiological level of insulin, plays crucial roles in the development and progression of diabetes, nonalcoholic fatty liver disease (NAFLD) and other diseases. So far, the distinct mechanism(s) of IR still needs further exploration. Long non-coding RNA (lncRNA) is a class of non-protein coding RNA molecules with a length greater than 200 nucleotides. LncRNAs are widely involved in many biological processes including cell differentiation, proliferation, apoptosis and metabolism. More recently, there has been increasing evidence that lncRNAs participated in the pathogenesis of IR, and the dysregulated lncRNA profile played important roles in the pathogenesis of metabolic diseases including obesity, diabetes and NAFLD. For example, the lncRNAs MEG3, H19, MALAT1, GAS5, lncSHGL and several other lncRNAs have been shown to regulate insulin signaling and glucose/lipid metabolism in various tissues. In this review, we briefly introduced the general features of lncRNA and the methods for lncRNA research, and then summarized and discussed the recent advances on the roles and mechanisms of lncRNAs in IR, particularly focused on liver, skeletal muscle and adipose tissues.

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Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity

Cited by 3 publications

References 68 publications

mTORC1 controls murine postprandial hepatic glycogen synthesis via Ppp1r3b

mTORC1 controls murine postprandial hepatic glycogen synthesis via Ppp1r3b

Emerging Roles and Potential Applications of Non-Coding RNAs in Cervical Cancer

Long Noncoding RNAs in the Pathogenesis of Insulin Resistance

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