Format

Send to

Choose Destination
Elife. 2018 Mar 12;7. pii: e33178. doi: 10.7554/eLife.33178.

ICE1 promotes the link between splicing and nonsense-mediated mRNA decay.

Author information

1
Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States.
2
National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, United States.

Abstract

The nonsense-mediated mRNA decay (NMD) pathway detects aberrant transcripts containing premature termination codons (PTCs) and regulates expression of 5-10% of non-aberrant human mRNAs. To date, most proteins involved in NMD have been identified by genetic screens in model organisms; however, the increased complexity of gene expression regulation in human cells suggests that additional proteins may participate in the human NMD pathway. To identify proteins required for NMD, we performed a genome-wide RNAi screen against >21,000 genes. Canonical members of the NMD pathway were highly enriched as top hits in the siRNA screen, along with numerous candidate NMD factors, including the conserved ICE1/KIAA0947 protein. RNAseq studies reveal that depletion of ICE1 globally enhances accumulation and stability of NMD-target mRNAs. Further, our data suggest that ICE1 uses a putative MIF4G domain to interact with exon junction complex (EJC) proteins and promotes the association of the NMD protein UPF3B with the EJC.

KEYWORDS:

ICE1; RNA quality control; UPF3B; biochemistry; chemical biology; chromosomes; exon junction complex; genes; human; nonsense-mediated mRNA decay; siRNA screen

PMID:
29528287
PMCID:
PMC5896957
DOI:
10.7554/eLife.33178
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center