Professional Education

  • Doctor of Philosophy, California Institute of Technology (2017)

All Publications

  • Structured elements drive extensive circular RNA translation. Molecular cell Chen, C. K., Cheng, R., Demeter, J., Chen, J., Weingarten-Gabbay, S., Jiang, L., Snyder, M. P., Weissman, J. S., Segal, E., Jackson, P. K., Chang, H. Y. 2021


    The human genome encodes tens of thousands circular RNAs (circRNAs) with mostly unknown functions. Circular RNAs require internal ribosome entry sites (IRES) if they are to undergo translation without a 5' cap. Here, we develop a high-throughput screen to systematically discover RNA sequences that can direct circRNA translation in human cells. We identify more than 17,000 endogenous and synthetic sequences as candidate circRNA IRES. 18S rRNA complementarity and a structured RNA element positioned on the IRES are important for driving circRNA translation. Ribosome profiling and peptidomic analyses show extensive IRES-ribosome association, hundreds of circRNA-encoded proteins with tissue-specific distribution, and antigen presentation. We find that circFGFR1p, a protein encoded by circFGFR1 that is downregulated in cancer, functions as a negative regulator of FGFR1 oncoprotein to suppress cell growth during stress. Systematic identification of circRNA IRES elements may provide important links among circRNA regulation, biological function, and disease.

    View details for DOI 10.1016/j.molcel.2021.07.042

    View details for PubMedID 34437836

  • Publisher Correction: A protein assembly mediates Xist localization and gene silencing. Nature Pandya-Jones, A., Markaki, Y., Serizay, J., Chitiashvili, T., Leon, W. R., Damianov, A., Chronis, C., Papp, B., Chen, C., McKee, R., Wang, X., Chau, A., Sabri, S., Leonhardt, H., Zheng, S., Guttman, M., Black, D. L., Plath, K. 2020


    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    View details for DOI 10.1038/s41586-020-2790-y

    View details for PubMedID 33005055

  • A protein assembly mediates Xist localization and gene silencing. Nature Pandya-Jones, A. n., Markaki, Y. n., Serizay, J. n., Chitiashvili, T. n., Mancia Leon, W. R., Damianov, A. n., Chronis, C. n., Papp, B. n., Chen, C. K., McKee, R. n., Wang, X. J., Chau, A. n., Sabri, S. n., Leonhardt, H. n., Zheng, S. n., Guttman, M. n., Black, D. L., Plath, K. n. 2020


    Nuclear compartments have diverse roles in regulating gene expression, yet the molecular forces and components that drive compartment formation remain largely unclear1. The long non-coding RNA Xist establishes an intra-chromosomal compartment by localizing at a high concentration in a territory spatially close to its transcription locus2 and binding diverse proteins3-5 to achieve X-chromosome inactivation (XCI)6,7. The XCI process therefore serves as a paradigm for understanding how RNA-mediated recruitment of various proteins induces a functional compartment. The properties of the inactive X (Xi)-compartment are known to change over time, because after initial Xist spreading and transcriptional shutoff a state is reached in which gene silencing remains stable even if Xist is turned off8. Here we show that the Xist RNA-binding proteins PTBP19, MATR310, TDP-4311 and CELF112 assemble on the multivalent E-repeat element of Xist7 and, via self-aggregation and heterotypic protein-protein interactions, form a condensate1 in the Xi. This condensate is required for gene silencing and for the anchoring of Xist to the Xi territory, and can be sustained in the absence of Xist. Notably, these E-repeat-binding proteins become essential coincident with transition to the Xist-independent XCI phase8, indicating that the condensate seeded by the E-repeat underlies the developmental switch from Xist-dependence to Xist-independence. Taken together, our data show that Xist forms the Xi compartment by seeding a heteromeric condensate that consists of ubiquitous RNA-binding proteins, revealing an unanticipated mechanism for heritable gene silencing.

    View details for DOI 10.1038/s41586-020-2703-0

    View details for PubMedID 32908311