A pinboard by
Francisco Fuentes

PhD student, Universidad de Concepción


Our aim is to understand better how translational control can affect cell viability during stress

Our cells require an acute control over which proteins are being synthesized and how much of it is bing made. This phenomenon is critical for maintaining any cell function, mediating the adequate cell response to changes in our tissues (the glucose availability or temperature) and even fluctuations in the environment, as the UV light exposure.

A common response to stressful conditions is the inhibition of protein synthesis, due to the high energy expend required to maintain it. When this happens, the molecules from which genetic information is translated into proteins (mRNAs) can be assembled into stable structures until the stressful conditions are gone.

One subset of these structures is called Stress Granules (SGs). SGs are believed to protect untranslated mRNAs from degradation and by doing so, cells do not need the de-novo synthesis of those mRNA molecules when stress is gone.

Our work is focused on how SG assembly can be modulated during stress to sustain cell viability, because it could have important repercussions in diseases in which the translational control is altered, like cancer and some mental disorders as schizophrenia.


Tumor protein D52 expression is post-transcriptionally regulated by T-cell intercellular antigen (TIA) 1 and TIA-related protein via mRNA stability.

Abstract: Although tumor protein D52 (TPD) family proteins were first identified nearly 20 years ago, their molecular regulatory mechanisms remain unclear. Therefore, we investigated the post-transcriptional regulation of TPD52 family genes. An RNA immunoprecipitation assay showed the potential binding ability of TPD52 family mRNAs to several RNA-binding proteins, and an RNA degradation assay revealed that TPD52 is subject to more prominent post-transcriptional regulation than TPD53 and 54. We subsequently focused on the 3'-untranslated region (3'-UTR) of TPD52 as a cis -acting element in post-transcriptional gene regulation. Several deletion mutants of the 3'-UTR of TPD52 mRNA were constructed and ligated to the 3' end of a reporter green fluorescence protein gene. RNA degradation assay revealed that a minimal cis -acting region, located in the 78-280 region of the 5'-proximal region of the 3'-UTR, stabilized the reporter mRNA. Biotin pull-down and RNA immunoprecipitation assays revealed specific binding of the region to T-cell intracellular antigen 1 (TIA-1) and TIA-1-related protein (TIAR). Knockdown of TIA-1/TIAR decreased not only the expression, but also the stability of TPD52 mRNA; it also decreased the expression and stability of the reporter gene ligated to the 3' end of the 78-280 fragment. Stimulation of TGF-b and EGF decreased the binding ability of these factors, resulted in decreased mRNA stability. These results indicate that the 78-280 fragment and TIA-1/TIAR concordantly contribute to mRNA stability as a cis -acting element and trans -acting factor(s), respectively. Thus, we herein report the specific interactions between these elements in the post-transcriptional regulation of the TPD52 gene.

Pub.: 17 Mar '17, Pinned: 30 Aug '17

Crystal structure of a dimerization domain of human Caprin-1: insights into the assembly of an evolutionarily conserved ribonucleoprotein complex consisting of Caprin-1, FMRP and G3BP1

Abstract: Caprin-1 plays roles in many important biological processes, including cellular proliferation, innate immune response, stress response and synaptic plasticity. Caprin-1 has been implicated in several human diseases, including osteosarcoma, breast cancer, viral infection, hearing loss and neurodegenerative disorders. The functions of Caprin-1 depend on its molecular-interaction network. Direct interactions have been established between Caprin-1 and the fragile X mental retardation protein (FMRP), Ras GAP-activating protein-binding protein 1 (G3BP1) and the Japanese encephalitis virus (JEV) core protein. Here, crystal structures of a fragment (residues 132–251) of Caprin-1, which adopts a novel all-α-helical fold and mediates homodimerization through a substantial interface, are reported. Homodimerization creates a large and highly negatively charged concave surface suggestive of a protein-binding groove. The FMRP-interacting sequence motif forms an integral α-helix in the dimeric Caprin-1 structure in such a way that the binding of FMRP would not disrupt the homodimerization of Caprin-1. Based on insights from the structures and existing biochemical data, the existence of an evolutionarily conserved ribonucleoprotein (RNP) complex consisting of Caprin-1, FMRP and G3BP1 is proposed. The JEV core protein may bind Caprin-1 at the negatively charged putative protein-binding groove and an adjacent E-rich sequence to hijack the RNP complex.

Pub.: 25 May '16, Pinned: 30 Aug '17