Date of Award

2008

Degree Type

Thesis

Department

Biological, Geological and Environmental Sciences

First Advisor

Mazumder, Barsanjit

Subject Headings

Protein binding, Ceruloplasmin, Cytology, Transcript-specific transaltional control, L13a, GAIT, Ceruloplasmin, eIF4G

Abstract

Transcript-specific translational control restricts macrophage inflammatory gene expression. The pero-inflammatory cytokine IFN-Îđ induces the phosphorylation of human ribosomal protein L13a and its subsequent release from 60S ribosome. L13a is a component of the interferon-gamma-activated inhibitor of translation (GAIT). The GAIT complex binds a defined element in the 3'-untranslated region (UTR) of ceruloplasmin (Cp) mRNA and causes delayed silencing of translation. In this research, we elucidate the molecular mechanism underlying L13a translational silencing activity. L13a mediates translational silencing particularly, when driven by internal ribosome entry sites (IRESs) that requires the initiation factor eIF4G, but is resistant to silencing when driven by eIF4F- independent IRESs. This demonstrates a critical role of the scaffold protein eIF4G. Global inhibition of protein synthesis by targeting eIF4G is well appreciated in virus infection and apoptosis however interaction of L13a with eIF4G blocks the 43S complex recruitment showing a unique role of eIF4G in gene specific translational silencing

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