Poster abstracts
Poster number 1 submitted by Rabab Abu Alhasan
Investigating UPF3 factors involvement in premature translation termination and recycling
Rabab Abu Alhasan (Department of Molecular Genetics), Zhongxia Yi (Department of Molecular Genetics), Sean Myers (Department of Physics), Ralf Bundschuh (Department of Physics)
Abstract:
The nonsense mediated decay (NMD) pathway is a surveillance pathway which detects faulty mRNAs with premature termination codons (PTC) and targets them for rapid decay to limit translation of truncated proteins. Naturally occurring mRNA can also undergo NMD as a way to regulate their abundance. Recognition of NMD-targeted mRNAs requires prematurely terminating ribosomes to be recognized by core NMD factors UPF1, UPF2, and UPF3. While UPF1 is the main NMD activator, the exact functions of UPF2 and UPF3 in the process are not well understood. Recent work from our lab suggests that UPF3 factors are non-essential but important enhancers of the NMD pathway. Additionally, since NMD is initiated by ribosomes stalled at PTCs, the process is expected to be coupled with ribosome termination and recycling. Our preliminary work, alongside previous publications, support the hypothesis that UPF3 factors are involved in enhancing termination and recycling at PTCs together with UPF1 and UPF2. We find that absence of UPF3 factors cause changes in the association of NMD factors with translating ribosomes. Additionally, cells lacking UPF3 show signs of inefficient termination such as increased ribosome collisions and decreased ribosome readthrough, which further supports potential UPF3 involvement in termination and recycling. To conclude, our work suggests that UPF3 factors play a role in enhancing NMD as well as premature termination and recycling. These results inspire future work to further investigate how the presence of UPF3 factors enhances termination and recycling, as well as which domains drive their differing functions. Methods such as selective ribosome footprinting, termination efficiency assays, and domain manipulation are planned for the future of this project.
References:
Yi, Z., Arvola, R., Myers, S., Dilsavor, C., Abu Alhasan, R. Carter, B., Patton, R., Bundschuh, R., Singh, G.(2021). Mammalian UPF3A and UPF3B activate NMD independently of their EJC binding bioRxiv doi.org/10.1101/2021.07.02.450872
Neu‐Yilik, G., Raimondeau, E., Eliseev, B., Yeramala, L., Amthor, B., Deniaud, A., Huard, K., Kerschgens, K., Hentze, M. W., Schaffitzel, C., & Kulozik, A. E. (2017). Dual function of Upf3b in early and late translation termination. The EMBO Journal, 36(20), 2968–2986.
Keywords: NMD, UPF3, Ribosome TerminationRecycling