Communication of the Position of Exon-Exon Junctions to the mRNA Surveillance Machinery by the Protein RNPS1

  title={Communication of the Position of Exon-Exon Junctions to the mRNA Surveillance Machinery by the Protein RNPS1},
  author={Jens Lykke-Andersen and M D Shu and Joan A. Steitz},
  pages={1836 - 1839}
In mammalian cells, splice junctions play a dual role in mRNA quality control: They mediate selective nuclear export of mature mRNA and they serve as a mark for mRNA surveillance, which subjects aberrant mRNAs with premature termination codons to nonsense-mediated decay (NMD). Here, we demonstrate that the protein RNPS1, a component of the postsplicing complex that is deposited 5′ to exon-exon junctions, interacts with the evolutionarily conserved human Upf complex, a central component of NMD… 

The nonsense-mediated decay RNA surveillance pathway.

Whether these proofreading events preferentially occur during a "pioneer" round of translation in higher and lower eukaryotes, their cellular location, and whether they can use alternative EJC factors or act independent of the EJC are discussed.

Splicing of U12-type introns deposits an exon junction complex competent to induce nonsense-mediated mRNA decay

In vitro splicing of a U12-type intron assembles an exon junction complex (EJC) that is comparably positioned and contains many of the same components as that deposited by the U2-type spliceosome.

Splicing enhances translation in mammalian cells: an additional function of the exon junction complex.

In mammalian cells, increased translational yield correlates with enhanced cytoplasmic polysome association of spliced mRNAs, and is attributable to deposition of exon junction complexes (EJCs).

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 Day in the Life of the Exon Junction Complex

The most important functions and main protagonists in the life of the exon junction complex are summarized and the latest findings on the assembly, composition and molecular activities of the EJC are provided.

No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors

The coexistence and function of different isoforms of up-frameshift protein 1 with an emphasis of their role at the endoplasmic reticulum and during stress are highlighted, underscoring that gene regulation by mammalian NMD is tightly controlled and context-dependent being conditional on developmental stage, tissue and cell types.



Should we kill the messenger? The role of the surveillance complex in translation termination and mRNA turnover

A model will be presented that suggests that the surveillance complex assesses translation termination by monitoring the transition of an RNP as it is converted from a nuclear to a cytoplasmic form during the initial rounds of translation.

Intron function in the nonsense-mediated decay of beta-globin mRNA: indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm.

It is proposed that the 3'-most exon-exon junction of beta-globin mRNA and, possibly, most mRNAs is marked by the removal of the 3-most intron during pre-mRNA splicing and that the "mark" accompanies mRNA during transport to the cytoplasm, which is remarkably consistent with which nonsense codons within the triosephosphate isomerase gene reduce TPI mRNA abundance.

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.

Mechanisms of mRNA surveillance in eukaryotes.

This proposed model for mRNA surveillance is similar to other systems of kinetic proofreading that monitor the accuracy of other biogenic processes such as translation and spliceosome assembly.

A mutated human homologue to yeast Upf1 protein has a dominant-negative effect on the decay of nonsense-containing mRNAs in mammalian cells.

It is demonstrated that expression of human Upf1 protein harboring an arginine-to-cysteine mutation at residue 844 within the RNA helicase domain acts in a dominant-negative fashion to abrogate the decay of nonsense-containing mRNA that takes place in association with nuclei or in the cytoplasm.