Role of the Nonsense-Mediated Decay Factor hUpf3 in the Splicing-Dependent Exon-Exon Junction Complex

  title={Role of the Nonsense-Mediated Decay Factor hUpf3 in the Splicing-Dependent Exon-Exon Junction Complex},
  author={V. Narry Kim and Naoyuki Kataoka and Gideon Dreyfuss},
  pages={1832 - 1836}
Nonsense-mediated messenger RNA (mRNA) decay, or NMD, is a critical process of selective degradation of mRNAs that contain premature stop codons. NMD depends on both pre-mRNA splicing and translation, and it requires recognition of the position of stop codons relative to exon-exon junctions. A key factor in NMD is hUpf3, a mostly nuclear protein that shuttles between the nucleus and cytoplasm and interacts specifically with spliced mRNAs. We found that hUpf3 interacts with Y14, a component of… 

Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells.

To isolate cellular complexes that are formed with Hupf1 and to explore the role of cellular proteins in NMD, a HeLa cell line is generated that stably expresses H up-frameshift protein 1 bearing a double-affinity tag and the association of poly(A)-binding protein with H upf1 is highly sensitive to treatment of the isolated complexes with RNase.

Nuclear Pnn/DRS Protein Binds to Spliced mRNPs and Participates in mRNA Processing and Export via Interaction with RNPS1

It is found that Pnn associates preferentially with mRNAs produced by splicing in vitro, and may participate, via its interaction with RNPS1, in mRNA metabolism in the nucleus, including mRNA splicing and export.

Stop codon-mediated suppression of splicing is a novel nuclear scanning mechanism not affected by elements of protein synthesis and NMD.

It is shown that SOS is a novel mechanism distinct from the known RNA surveillance mechanisms because it is not dependent on translation and is not affected by RNAi-mediated down-regulation of h upf1 and hUpf2--two key components of the NMD pathway.

Regulation of Multiple Core Spliceosomal Proteins by Alternative Splicing-Coupled Nonsense-Mediated mRNA Decay

The results show that AS-coupled NMD can have different UPF factor requirements and is likely to regulate many general components of the spliceosome, and conserved, PTC-introducing AS events are enriched in genes that encode core spliceOSomal proteins.

The Interaction between Cap-binding Complex and RNA Export Factor Is Required for Intronless mRNA Export*

Analysis of the RNA-binding protein complexes revealed that REF associates with β-globin mRNA at the region other than the EJC deposition site, and co-injection of CBP20 and REF may play a stimulatory role to export the capped intronless mRNAs.

Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay.

The SMG-1-mediated phosphorylation of Upf1 occurs on the association of SURF with EJC, which provides the link between the EJC and recognition of PTCs and triggers NMD.

5' exon interactions within the human spliceosome establish a framework for exon junction complex structure and assembly.

A general consequence of pre-mRNA splicing is the stable deposition of several proteins 20-24 nucleotides (nt) upstream of exon-exon junctions on spliced mRNAs. This exon junction complex (EJC)



A human RNA helicase-like protein, HRH1, facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome.

The arginine/serine-rich domain of HRH1, which is missing in Prp22, confers a nuclear localization signal, and appears to facilitate the interaction ofHRH1 with the spliceosome, the first report on a bona fide mammalian homolog of yeast Prp splicing factor, and also on a mammalian RNA helicase-likesplicing factor.

The spliceosome deposits multiple proteins 20–24 nucleotides upstream of mRNA exon–exon junctions

It is reported that the spliceosome stably deposits several proteins on mRNAs, probably as a single complex of ∼335 kDa, which protects 8 nucleotides of mRNA from complete RNase digestion at a conserved position 20–24 nucleotide upstream of exon–exon junctions.

A Premature Termination Codon Interferes with the Nuclear Function of an Exon Splicing Enhancer in an Open Reading Frame-Dependent Manner

It is suggested that a PTC can interfere with the function of an exon splicing enhancer in an open reading frame-dependent manner and that the PTC is recognized in the nucleus.

Splicing is required for rapid and efficient mRNA export in metazoans.

  • M. LuoR. Reed
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
A link between splicing and efficient mRNA export is revealed, which may explain the reports that an intron is required for efficient expression of many protein-coding genes in metazoans.

Pre-mRNA splicing alters mRNP composition: evidence for stable association of proteins at exon-exon junctions.

The results demonstrate that the spliceosome can leave behind signature proteins at exon-exon junctions, which could influence downstream metabolic events in vivo such as mRNA transport, translation, and nonsense-mediated decay.

A coactivator of pre-mRNA splicing.

The results suggest that a complex of the nuclear matrix proteins SRm160 and SRm300 functions as a coactivator of pre-mRNA splicing.

Identification of a novel component of the nonsense-mediated mRNA decay pathway by use of an interacting protein screen.

The identification and characterization of NMD2, a yeast gene that encodes a specific Upf1p-interacting protein and the association of a dominant-negative phenotype with a gene fragment identified in a two-hybrid screen suggests a generalized approach to confirming the function of genes identified in such screens.