Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation.

Article Details

Citation

Sampath P, Mazumder B, Seshadri V, Gerber CA, Chavatte L, Kinter M, Ting SM, Dignam JD, Kim S, Driscoll DM, Fox PL

Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation.

Cell. 2004 Oct 15;119(2):195-208.

PubMed ID
15479637 [ View in PubMed
]
Abstract

Aminoacyl tRNA synthetases (ARS) catalyze the ligation of amino acids to cognate tRNAs. Chordate ARSs have evolved distinctive features absent from ancestral forms, including compartmentalization in a multisynthetase complex (MSC), noncatalytic peptide appendages, and ancillary functions unrelated to aminoacylation. Here, we show that glutamyl-prolyl-tRNA synthetase (GluProRS), a bifunctional ARS of the MSC, has a regulated, noncanonical activity that blocks synthesis of a specific protein. GluProRS was identified as a component of the interferon (IFN)-gamma-activated inhibitor of translation (GAIT) complex by RNA affinity chromatography using the ceruloplasmin (Cp) GAIT element as ligand. In response to IFN-gamma, GluProRS is phosphorylated and released from the MSC, binds the Cp 3'-untranslated region in an mRNP containing three additional proteins, and silences Cp mRNA translation. Thus, GluProRS has divergent functions in protein synthesis: in the MSC, its aminoacylation activity supports global translation, but translocation of GluProRS to an inflammation-responsive mRNP causes gene-specific translational silencing.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Bifunctional glutamate/proline--tRNA ligaseP07814Details
Glyceraldehyde-3-phosphate dehydrogenaseP04406Details
60S ribosomal protein L13aP40429Details