RGD Reference Report - Tristetraprolin and its family members can promote the cell-free deadenylation of AU-rich element-containing mRNAs by poly(A) ribonuclease. - Rat Genome Database

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Tristetraprolin and its family members can promote the cell-free deadenylation of AU-rich element-containing mRNAs by poly(A) ribonuclease.

Authors: Lai, WS  Kennington, EA  Blackshear, PJ 
Citation: Lai WS, etal., Mol Cell Biol. 2003 Jun;23(11):3798-812.
RGD ID: 11344945
Pubmed: PMID:12748283   (View Abstract at PubMed)
PMCID: PMC155217   (View Article at PubMed Central)

Eukaryotic mRNA stability can be influenced by AU-rich elements (AREs) within mRNA primary sequences. Tristetraprolin (TTP) is a CCCH tandem zinc finger protein that binds to ARE-containing transcripts and destabilizes them, apparently by first promoting the removal of their poly(A) tails. We developed a cell-free system in which TTP and its related proteins stimulated the deadenylation of ARE-containing, polyadenylated transcripts. Transcript deadenylation was not stimulated when a mutant TTP protein was used that was incapable of RNA binding, nor when a mutant ARE was present that did not bind TTP. The ability of TTP to promote transcript deadenylation required Mg(2+), but not ATP or prior capping of the RNA substrate. Cotransfection and additivity studies with the poly(A) RNase (PARN) demonstrated that TTP promoted the ability of this enzyme to deadenylate ARE-containing, polyadenylated transcripts, while having no effect on transcripts lacking an ARE. There was no effect of TTP to act synergistically with enzymatically inactive PARN mutants. We conclude that TTP can promote the deadenylation of ARE-containing, polyadenylated substrates by PARN. This interaction may be responsible for the ability of TTP and its family members to promote the deadenylation of such transcripts in intact cells.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Zfp36l1Ratpositive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay involved_inIDA PMID:12748283UniProt 
Zfp36l1Ratregulation of mRNA stability involved_inIDA PMID:12748283UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Zfp36l1RatmRNA 3'-UTR AU-rich region binding enablesIDA PMID:12748283UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Zfp36l1  (zinc finger protein 36, C3H type-like 1)


Additional Information