Helmholtz Gemeinschaft


CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplementary Data)

Item Type:Article
Title:CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex
Creators Name:Gerbracht, J.V. and Boehm, V. and Britto-Borges, T. and Kallabis, S. and Wiederstein, J.L. and Ciriello, S. and Aschemeier, D.U. and Krüger, M. and Frese, C.K. and Altmüller, J. and Dieterich, C. and Gehring, N.H.
Abstract:The exon junction complex (EJC) is an essential constituent and regulator of spliced messenger ribonucleoprotein particles (mRNPs) in metazoans. As a core component of the EJC, CASC3 was described to be pivotal for EJC-dependent nuclear and cytoplasmic processes. However, recent evidence suggests that CASC3 functions differently from other EJC core proteins. Here, we have established human CASC3 knockout cell lines to elucidate the cellular role of CASC3. In the knockout cells, overall EJC composition and EJC-dependent splicing are unchanged. A transcriptome-wide analysis reveals that hundreds of mRNA isoforms targeted by nonsense-mediated decay (NMD) are upregulated. Mechanistically, recruiting CASC3 to reporter mRNAs by direct tethering or via binding to the EJC stimulates mRNA decay and endonucleolytic cleavage at the termination codon. Building on existing EJC-NMD models, we propose that CASC3 equips the EJC with the persisting ability to communicate with the NMD machinery in the cytoplasm. Collectively, our results characterize CASC3 as a peripheral EJC protein that tailors the transcriptome by promoting the degradation of EJC-dependent NMD substrates.
Keywords:Amino Acid Sequence, Cell Nucleus, Exons, Gene Knockout Techniques, Messenger RNA, Neoplasm Proteins, Nonsense Mediated mRNA Decay, Ribonucleoproteins, RNA Splicing, RNA-Binding Proteins, Transcriptome
Source:Nucleic Acids Research
Publisher:Oxford University Press
Page Range:8626-8644
Date:4 September 2020
Official Publication:https://doi.org/10.1093/nar/gkaa564
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library