Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Human UPF3A and UPF3B enable fault-tolerant activation of nonsense-mediated mRNA decay

[img]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB
[img] Other (Supporting Information)
121MB

Item Type:Article
Title:Human UPF3A and UPF3B enable fault-tolerant activation of nonsense-mediated mRNA decay
Creators Name:Wallmeroth, D. and Lackmann, J.W. and Kueckelmann, S. and Altmüller, J. and Dieterich, C. and Boehm, V. and Gehring, N.H.
Abstract:The paralogous human proteins UPF3A and UPF3B are involved in recognizing mRNAs targeted by nonsense-mediated mRNA decay (NMD). UPF3B has been demonstrated to support NMD, presumably by bridging an exon junction complex (EJC) to the NMD factor UPF2. The role of UPF3A has been described either as a weak NMD activator or an NMD inhibitor. Here, we present a comprehensive functional analysis of UPF3A and UPF3B in human cells using combinatory experimental approaches. Overexpression or knockout of UPF3A as well as knockout of UPF3B did not substantially change global NMD activity. In contrast, the co-depletion of UPF3A and UPF3B resulted in a marked NMD inhibition and a transcriptome-wide upregulation of NMD substrates, demonstrating a functional redundancy between both NMD factors. In rescue experiments, UPF2 or EJC binding-deficient UPF3B largely retained NMD activity. However, combinations of different mutants, including deletion of the middle domain, showed additive or synergistic effects and therefore failed to maintain NMD. Collectively, UPF3A and UPF3B emerge as fault-tolerant, functionally redundant NMD activators in human cells.
Keywords:Gene Paralogs, mRNA Turnover, Nonsense-Mediated mRNA Decay, UPF3
Source:EMBO Journal
ISSN:0261-4189
Publisher:Nature Publishing Group
Volume:41
Number:10
Page Range:e109191
Date:16 May 2022
Official Publication:https://doi.org/10.15252/embj.2021109191
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library