The studies in this Project focus on understanding the RBPs and ncRNAs that influence energy metabolism, since the processes that generate energy become impaired with aging. In particular, we have studied the regulation of insulin production, adipogenesis, and autophagy by RBPs and ncRNAs. Glucose homeostasis. With rising appreciation that glucose metabolism is extensively regulated at the post-transcriptional level, we recently identified the HuD as an RBP that associated with the 5UTR of the mRNA encoding insulin and repressed insulin translation (Lee et al., Mol Cell 2012). Accordingly, HuD-null mice had higher levels of insulin, while HuD-overexpressing mice showed lower circulating insulin and displayed a reduced ability to uptake glucose in tissues (Lee et al., Mol Cell 2012). More recently, in collaboration with the Fernndez-Hernando laboratory (New York University), we reported that miR-33 is another key player in glucose homeostasis (Ramirez et al., Mol Cell Biol 2013). On the topic of adipogenesis, we are pursuing further analysis of two microRNAs differentially expressed during adipose tissue differentiation: miR-130a and miR-130b (Lee et al., 2011). Other energy metabolism. During this review period, we also discovered that miR-519, a microRNA that shows increased levels with senescence and targets the HuR mRNA, was a potent trigger of autophagy and a growth repressor (Abdelmohsen et al., Mol Cell Biol 2012). As part of another long-standing initiative to understand the influence of sirtuins on senescence and aging, we collaborated with the de Cabo laboratory (TGB, NIA) in reporting that the sirtuin activator SRT1720 affected mitochondrial respiration and improved the survival and healthspan of obese mice (Minor et al., Sci Reports 2012).

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000394-06
Application #
8736557
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$481,978
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Di Francesco, Andrea; Di Germanio, Clara; Panda, Amaresh C et al. (2016) Novel RNA-binding activity of NQO1 promotes SERPINA1 mRNA translation. Free Radic Biol Med 99:225-233
Lastres-Becker, Isabel; Nonis, David; Eich, Florian et al. (2016) Mammalian ataxin-2 modulates translation control at the pre-initiation complex via PI3K/mTOR and is induced by starvation. Biochim Biophys Acta 1862:1558-69
Noh, Ji Heon; Kim, Kyoung Mi; Abdelmohsen, Kotb et al. (2016) HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP. Genes Dev 30:1224-39
Panda, Amaresh C; Abdelmohsen, Kotb; Martindale, Jennifer L et al. (2016) Novel RNA-binding activity of MYF5 enhances Ccnd1/Cyclin D1 mRNA translation during myogenesis. Nucleic Acids Res 44:2393-408
Kim, Jiyoung; Kim, Kyoung Mi; Noh, Ji Heon et al. (2016) Long noncoding RNAs in diseases of aging. Biochim Biophys Acta 1859:209-21
Lee, Kwang-Pyo; Shin, Yeo Jin; Panda, Amaresh C et al. (2015) miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4. Genes Dev 29:1605-17
Panda, Amaresh C; Abdelmohsen, Kotb; Yoon, Je-Hyun et al. (2014) RNA-binding protein AUF1 promotes myogenesis by regulating MEF2C expression levels. Mol Cell Biol 34:3106-19
Cammas, Anne; Sanchez, Brenda Janice; Lian, Xian Jin et al. (2014) Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation. Nat Commun 5:4190
Panda, Amaresh C; Sahu, Itishri; Kulkarni, Shardul D et al. (2014) miR-196b-mediated translation regulation of mouse insulin2 via the 5'UTR. PLoS One 9:e101084
Ramírez, Cristina M; Lin, Chin Sheng; Abdelmohsen, Kotb et al. (2014) RNA binding protein HuR regulates the expression of ABCA1. J Lipid Res 55:1066-76

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