RGD Reference Report - Identification of a signature motif for the eIF4a3-SECIS interaction. - Rat Genome Database

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Identification of a signature motif for the eIF4a3-SECIS interaction.

Authors: Budiman, ME  Bubenik, JL  Driscoll, DM 
Citation: Budiman ME, etal., Nucleic Acids Res. 2011 Sep 1;39(17):7730-9. doi: 10.1093/nar/gkr446. Epub 2011 Jun 17.
RGD ID: 10044260
Pubmed: PMID:21685449   (View Abstract at PubMed)
PMCID: PMC3177196   (View Article at PubMed Central)
DOI: DOI:10.1093/nar/gkr446   (Journal Full-text)

eIF4a3, a DEAD-box protein family member, is a component of the exon junction complex which assembles on spliced mRNAs. The protein also acts as a transcript-selective translational repressor of selenoprotein synthesis during selenium deficiency. Selenocysteine (Sec) incorporation into selenoproteins requires a Sec Insertion Sequence (SECIS) element in the 3' untranslated region. During selenium deficiency, eIF4a3 binds SECIS elements from non-essential selenoproteins, preventing Sec insertion. We identified a molecular signature for the eIF4a3-SECIS interaction using RNA gel shifts, surface plasmon resonance and enzymatic foot printing. Our results support a two-site interaction model, where eIF4a3 binds the internal and apical loops of the SECIS. Additionally, the stability of the complex requires uridine in the SECIS core. In terms of protein requirements, the two globular domains of eIF4a3, which are connected by a linker, are both critical for SECIS binding. Compared to full-length eIF4a3, the two domains in trans bind with a lower association rate but notably, the uridine is no longer important for complex stability. These results provide insight into how eIF4a3 discriminates among SECIS elements and represses translation.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Eif4a3Ratnegative regulation of selenocysteine incorporation  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Eif4a3RatRNA stem-loop binding  IDA  RGD 
Eif4a3Ratselenocysteine insertion sequence binding  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Eif4a3  (eukaryotic translation initiation factor 4A3)


Additional Information