Several studies are underway in the RNA Regulation Section to investigate the RBPs and ncRNAs that influence neuronal physiology and pathology, with particular emphasis on neurodegeneration. During this review period, we have studied the role of several RBPs and ncRNAs implicated in Alzheimers disease (AD) and Parkinsons disease (PD), as well as other pathologies of the nervous system. We recently reported that the levels of amyloid precursor protein (APP), which is cleaved to release the Alzheimers disease hallmark peptide A, was regulated by RBPs FMRP (fragile X mental retardation protein) and hnRNP C (heterogeneous nuclear ribonucleoprotein C). We further discovered that FMRP and hnRNPC associated with the coding region of APP mRNA in a competitive manner and repressed or enhanced APP translation, respectively. Expanding upon this work, we collaborated with Weidong Wangs group (LG, NIA), in studies that revealed that FMRP function was modulated by a novel RNA topoisomerase activity Xu et al., Nat. Neurosci 2013. We have also continued collaborative studies with the Cookson laboratory (LNG, NIA), aimed at elucidating the function of the Parkinsons disease-associated protein DJ-1. Prominent among DJ-1 target mRNAs were those encoding proteins that regulate mitochondrial metabolism. During this review period, we have continued to study the RBP HuD, which is found primarily in neuronal tissues and was negatively regulated by the microRNA miR-375. Further studies have focused on other cell types in the nervous system;for example, in collaboration with the Woodhoo lab (BioGune, Spain), we reported that the HuD-related protein HuR was linked to development of Schwann cells Iruarrizaga-Lejarreta et al., J. Neuroscience, 2012 and in collaboration with the Mattson lab (LNS, NIA), miR-181 was identified as a key mediator in the neuroinflammatory response of astrocytes Hutchison et al., 2013.
| Idda, M Laura; Munk, Rachel; Abdelmohsen, Kotb et al. (2018) Noncoding RNAs in Alzheimer's disease. Wiley Interdiscip Rev RNA 9: |
| Grammatikakis, Ioannis; Abdelmohsen, Kotb; Gorospe, Myriam (2017) Posttranslational control of HuR function. Wiley Interdiscip Rev RNA 8: |
| Grammatikakis, Ioannis; Zhang, Peisu; Mattson, Mark P et al. (2016) The long and the short of TRF2 in neurogenesis. Cell Cycle 15:3026-3032 |
| Grammatikakis, Ioannis; Zhang, Peisu; Panda, Amaresh C et al. (2016) Alternative Splicing of Neuronal Differentiation Factor TRF2 Regulated by HNRNPH1/H2. Cell Rep 15:926-934 |
| Grammatikakis, Ioannis; Gorospe, Myriam (2016) Identification of neural stem cell differentiation repressor complex Pnky-PTBP1. Stem Cell Investig 3:10 |
| Ahmad, Muzammil; Xue, Yutong; Lee, Seung Kyu et al. (2016) RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals. Nucleic Acids Res 44:6335-49 |
| Uren, Philip J; Vo, Dat T; de Araujo, Patricia Rosa et al. (2015) RNA-Binding Protein Musashi1 Is a Central Regulator of Adhesion Pathways in Glioblastoma. Mol Cell Biol 35:2965-78 |
| Zhang, Peisu; Abdelmohsen, Kotb; Liu, Yong et al. (2015) Novel RNA- and FMRP-binding protein TRF2-S regulates axonal mRNA transport and presynaptic plasticity. Nat Commun 6:8888 |
| Yoon, Je-Hyun; Gorospe, Myriam (2014) Ribonucleoprotein therapy in Alzheimer's disease? Aging (Albany NY) 6:428-9 |
| Hutchison, Emmette R; Kawamoto, Elisa M; Taub, Dennis D et al. (2013) Evidence for miR-181 involvement in neuroinflammatory responses of astrocytes. Glia 61:1018-28 |
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