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


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.

SUBMITTER: Baird TD 

PROVIDER: S-EPMC5896957 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Baird Thomas D TD   Cheng Ken Chih-Chien KC   Chen Yu-Chi YC   Buehler Eugen E   Martin Scott E SE   Inglese James J   Hogg J Robert JR  

eLife 20180312


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  ...[more]

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