Characterizing Interactions between the RNA exosome and MYCN/NEXT complex

Characterizing Interactions between the RNA exosome and MYCN/NEXT complex

Document Type

Poster

Publication Date

Fall 10-1-2026

Abstract

MYCN is canonically a transcription factor that is also involved in other cellular processes, including ribosome biogenesis and cell cycle control. Amplification of the MYCN gene can lead to high-risk neuroblastoma, as it inhibits cell differentiation and apoptosis while activating transcriptional and metabolic pathways that support tumor growth and survival. However, direct inhibition of MYCN has been difficult because the protein is intrinsically disordered in its monomeric state. To overcome this difficulty, an alternative strategy was proposed to target MYCN while it is in complex with its protein partners. Our lab and collaborators have identified several proteins and protein complexes essential for MYCN-driven tumor growth, including the RNA exosome and one of its adaptors, the Nuclear Exosome Targeting (NEXT) complex. The goal of this project was to verify and characterize the interactions between MYCN and the RNA exosome, as well as between the RNA exosome and the NEXT complex, to better understand how MYCN can associate with these protein complexes. To identify direct interactions of the RNA exosome with MYCN and the NEXT complex, we individually purified each RNA exosome subunit and performed pull-down assays. We then used size exclusion chromatography to reconstitute the full complex. We found that both EXOSC2, the RNA exosome ‘cap’ subunit, and the EXOSC10-C1D pair, an enzymatic component of the exosome, interact with MYCN, with EXOSC2 associating with multiple domains of MYCN. Both subunits also interact with the NEXT complex, with EXOSC2 interacting with ZCCHC8 and RBM7 subunits, and EXOSC10-C1D interacting with MTR4.

Department

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA

Project Mentor

Dr. Alexandra D'Ordine, Dr. Seychelle M. Vos

Funding and Acknowledgements

I would like to thank all members of the Vos lab for welcoming me in the lab and being supportive throughout the 10 weeks. A special thank you to Alexandra D’Ordine for mentoring me during the entire process from teaching me molecular biology, preparing the protocols, and for purifying all non-RNA Exosome proteins. I also want to thank Seychelle M. Vos for providing me the opportunity to learn in the Vos lab. In terms of the MSRP Bio program, I would like to thank Mandana Sassanfar and Paloma Kuralic for organizing the MSRP bio program. Funding provided by Bernard S. and Sophie G. Gould Fund.

Characterizing Interactions between the RNA exosome and MYCN/NEXT complex

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