Research Departments & Organizations
Amyotrophic Lateral Sclerosis; Computational Biology; Frontotemporal Dementia; Genomics; High-Throughput Nucleotide Sequencing; Molecular Biology; Motor Neuron Disease; Neurodegenerative Diseases; Neurons; RNA; RNA Transport; RNA-Binding Proteins
The Guo lab is broadly interested in questions at the intersection of neuroscience and RNA biology. Current research in the lab is focused on the roles of RNA structures in neural development, homeostasis, and neurodegenerative diseases, taking a combination of computational, biochemical, genetic, and genomic approaches.
Extensive Research Description
1. Pathogenic RNA repeats
A variety of neurological disorders, including myotonic dystrophy, amyotrophic lateral sclerosis, and frontotemporal dementia, are caused by the expansion of nucleotide repeats in the human genome. The repeat-containing RNAs transcribed from these loci exhibit unique properties. For example, some RNA repeats undergo phase separation and form distinct foci, which may sequester essential RNA-binding proteins. Some RNA repeats are translated into toxic polypeptides via a noncanonical mechanism. We aim to determine whether and how the structures formed by RNA repeats may contribute to their unusual properties and the associated disease symptoms, with the goal of developing novel diagnostics and therapeutics.
2. Localization of neuronal mRNAs
Spatially precise regulation of gene expression is critical for morphologically complex cells. In neurons, this is achieved in part through the localization of mRNAs to distal compartments in dendrites and axons. Although mRNA localization and local translational control are known to play important roles in neuronal development and plasticity, we do not fully understand the cis-regulatory elements (often being secondary structures) in mRNAs that determine their localization and how these elements function. We aim to systematically identify these structural elements as well as the trans-acting factors that mediate their functions.
3. Noncoding RNA functions in neural development
Since the advent of high-throughput DNA sequencing technologies, the identification of the cellular repertoire of noncoding RNAs has vastly outpaced our understanding of their biological functions. Of the many thousands of small RNAs and long noncoding RNAs in cells, only a small fraction has been functionally characterized. We are interested in developing new tools to interrogate their functions during development of the mammalian nervous system.
RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria.
Guo JU, Bartel DP. RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria. Science (New York, N.Y.) 2016, 353. 2016
Expanded identification and characterization of mammalian circular RNAs.
Guo JU, Agarwal V, Guo H, Bartel DP. Expanded identification and characterization of mammalian circular RNAs. Genome Biology 2014, 15:409. 2014
Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain.
Guo JU, Su Y, Shin JH, Shin J, Li H, Xie B, Zhong C, Hu S, Le T, Fan G, Zhu H, Chang Q, Gao Y, Ming GL, Song H. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nature Neuroscience 2014, 17:215-22. 2014
Neuronal activity modifies the DNA methylation landscape in the adult brain.
Guo JU, Ma DK, Mo H, Ball MP, Jang MH, Bonaguidi MA, Balazer JA, Eaves HL, Xie B, Ford E, Zhang K, Ming GL, Gao Y, Song H. Neuronal activity modifies the DNA methylation landscape in the adult brain. Nature Neuroscience 2011, 14:1345-51. 2011
Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain.
Guo JU, Su Y, Zhong C, Ming GL, Song H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 2011, 145:423-34. 2011