Junjie Guo, PhD

1. RNA dysregulation in neurodegenerative diseases

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 repeat sequences in the genome. These mutations can interfere with gene expression and cause neurotoxicity through a variety of mechanisms. We apply molecular and genomic approaches in patient-derived stem cells and neuronal models to investigate these mechanisms and how they impact diseases, with the goal of developing novel therapeutics.

Read more:

Yang S et al, Aberrant splicing exonizes C9orf72 repeat expansion in ALS/FTD. Nat Neurosci. 2025 Oct;28(10):2034-2043. doi: 10.1038/s41593-025-02039-5. PMID: 40790269

Yang S, Lei Z, Guo JU. TDP-43 loss brings RNA to a twist ending. Nat Neurosci. 2025 Nov;28(11):2176-2177. doi: 10.1038/s41593-025-02065-3.PMID: 41120749

Sun Y, et al, C9orf72 arginine-rich dipeptide repeats inhibit UPF1-mediated RNA decay via translational repression. Nat Commun. 2020 Jul 3;11(1):3354. doi: 10.1038/s41467-020-17129-0.PMID: 32620797

2. Noncanonical mRNA translation in neuronal development and functions

In contrast to the "one mRNA, one protein" dogma, some cellular and viral mRNAs can encode more than one protein isoform. We have recently discovered that mRNAs encoding synaptic organizers, including neuronal pentraxin receptor (NPR) and C1q-like protein family, can produce two distinctly localized protein isoforms by having two alternative translation initiation sites. Using primary neurons and genetically engineered mouse models, we are identifying novel roles of alternative mRNA translation in generating diverse synaptic protein isoforms to support neural circuit functions.

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Lee PJ et al, Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions. Mol Cell. 2024 Oct 17;84(20):3967-3978.e8. doi: 10.1016/j.molcel.2024.08.032. Epub 2024 Sep 23.PMID: 39317199

Sun Y et al, Restriction of SARS-CoV-2 replication by targeting programmed -1 ribosomal frameshifting. PNAS. 2021 Jun 29;118(26):e2023051118. doi: 10.1073/pnas.2023051118.PMID: 34185680

Wei LH, Guo JU. Coding functions of "noncoding" RNAs. Science. 2020 Mar 6;367(6482):1074-1075. doi: 10.1126/science.aba6117.PMID: 32139529