Junjie Guo, PhD
Research & Publications
The Guo lab studies RNA regulation in health and diseases of the nervous system, taking a combination of computational, biochemical, genetic, and genomic approaches.
Extensive Research Description
1. RNA dysregulation in nucleotide repeat expansion-associated neurodegeneration
An increasing number of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have been linked to the instability and expansion of nucleotide repeats in the genome, involving a variety of disease mechanisms. For example, some repeat sequences interfere with transcription and pre-mRNA processing. Some repeat RNAs form aggregates and sequester RNA-binding proteins. Others are translated into toxic polypeptides. We aim to determine the causes of these distinctive properties and how they impact disease, with the goal of developing new therapeutics.
2. Noncanonical translation mechanisms
Deviations from canonical translation can occur during each step of mRNA translation (initiation, elongation, and termination). For example, initiation at non-AUG codons plays important roles in regulating canonical translation in normal cells, but also causes the production of toxic peptide from repeat RNAs in neurological disorders. Many RNA viruses employ ribosomal frameshifting to regulate translation of essential viral proteins. We are investigating both physiological and pathological roles of these noncanonical translation mechanisms.
3. Neuronal mRNA transport and local translation
In polarized cells like neurons, newly transcribed mRNAs are often trafficked to distinct subcellular locations (e.g., dendrites and axon), where they can be locally translated in response to external stimuli. We are developing novel technologies that can help better understand the spatial and temporal regulation of mRNA transport and local translation.
Amyotrophic Lateral Sclerosis; Neurons; RNA; Motor Neuron Disease; RNA-Binding Proteins; Computational Biology; Neurodegenerative Diseases; Genomics; RNA Transport; Frontotemporal Dementia; High-Throughput Nucleotide Sequencing
- Stress promotes RNA G-quadruplex folding in human cellsKharel P, Fay M, Manasova E, Anderson P, Kurkin A, Guo J, Ivanov P. Stress promotes RNA G-quadruplex folding in human cells Nature Communications 2023, 14: 205. PMID: 36639366, PMCID: PMC9839774, DOI: 10.1038/s41467-023-35811-x.
- Systematic generation and imaging of tandem repeats reveal base-pairing properties that promote RNA aggregationIsiktas A, Eshov A, Yang S, Guo J. Systematic generation and imaging of tandem repeats reveal base-pairing properties that promote RNA aggregation Cell Reports Methods 2022, 2: 100334. PMID: 36452875, PMCID: PMC9701603, DOI: 10.1016/j.crmeth.2022.100334.
- Secondary structural ensembles of the SARS-CoV-2 RNA genome in infected cellsLan TCT, Allan MF, Malsick LE, Woo JZ, Zhu C, Zhang F, Khandwala S, Nyeo SSY, Sun Y, Guo JU, Bathe M, Näär A, Griffiths A, Rouskin S. Secondary structural ensembles of the SARS-CoV-2 RNA genome in infected cells Nature Communications 2022, 13: 1128. PMID: 35236847, PMCID: PMC8891300, DOI: 10.1038/s41467-022-28603-2.
- Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshiftingSun Y, Abriola L, Niederer RO, Pedersen SF, Alfajaro MM, Silva Monteiro V, Wilen CB, Ho YC, Gilbert WV, Surovtseva YV, Lindenbach BD, Guo JU. Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2023051118. PMID: 34185680, PMCID: PMC8256030, DOI: 10.1073/pnas.2023051118.
- Regulation of nonsense-nediated mRNA decay in neural development and diseaseLee PJ, Yang S, Sun Y, Guo JU. Regulation of nonsense-nediated mRNA decay in neural development and disease Journal Of Molecular Cell Biology 2021, 13: mjab022-. PMID: 33783512, PMCID: PMC8339359, DOI: 10.1093/jmcb/mjab022.
- C9orf72 arginine-rich dipeptide repeats inhibit UPF1-mediated RNA decay via translational repressionSun Y, Eshov A, Zhou J, Isiktas AU, Guo JU. C9orf72 arginine-rich dipeptide repeats inhibit UPF1-mediated RNA decay via translational repression Nature Communications 2020, 11: 3354. PMID: 32620797, PMCID: PMC7335171, DOI: 10.1038/s41467-020-17129-0.
- Coding functions of “noncoding” RNAsWei LH, Guo JU. Coding functions of “noncoding” RNAs Science 2020, 367: 1074-1075. PMID: 32139529, DOI: 10.1126/science.aba6117.
- 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 PMID: 27708011, PMCID: PMC5367264, DOI: 10.1126/science.aaf5371.
- 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. PMID: 25070500, PMCID: PMC4165365, DOI: 10.1186/s13059-014-0409-z.
- 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. PMID: 24362762, PMCID: PMC3970219, DOI: 10.1038/nn.3607.
- Neuronal activation and insight into the plasticity of DNA methylation.Felling RJ, Guo JU, Song H. Neuronal activation and insight into the plasticity of DNA methylation. Epigenomics 2012, 4: 125-7. PMID: 22449183, DOI: 10.2217/epi.12.2.
- Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia.Kang E, Burdick KE, Kim JY, Duan X, Guo JU, Sailor KA, Jung DE, Ganesan S, Choi S, Pradhan D, Lu B, Avramopoulos D, Christian K, Malhotra AK, Song H, Ming GL. Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia. Neuron 2011, 72: 559-71. PMID: 22099459, DOI: 10.1016/j.neuron.2011.09.032.
- 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. PMID: 21874013, PMCID: PMC3183401, DOI: 10.1038/nn.2900.
- 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. PMID: 21496894, PMCID: PMC3088758, DOI: 10.1016/j.cell.2011.03.022.
- Epigenetic choreographers of neurogenesis in the adult mammalian brain.Ma DK, Marchetto MC, Guo JU, Ming GL, Gage FH, Song H. Epigenetic choreographers of neurogenesis in the adult mammalian brain. Nat Neurosci 2010, 13: 1338-44. PMID: 20975758, DOI: 10.1038/nn.2672.
- DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212.Kim JY, Duan X, Liu CY, Jang MH, Guo JU, Pow-anpongkul N, Kang E, Song H, Ming GL. DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron 2009, 63: 761-73. PMID: 19778506, DOI: 10.1016/j.neuron.2009.08.008.