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The RNA-binding protein Fus directs translation of localized mRNAs in APC-RNP granules. | LitMetric

The RNA-binding protein Fus directs translation of localized mRNAs in APC-RNP granules.

J Cell Biol

Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Published: December 2013

AI Article Synopsis

  • RNA localization pathways guide mRNAs to specific cell areas, influencing various physiological processes, with the tumor-suppressor protein APC facilitating RNA transport to cell protrusions.
  • The RNA-binding protein Fus/TLS is not needed for the localization of APC-RNPs but is crucial for their effective translation, especially within protrusions.
  • Mutations in Fus, linked to ALS, lead to the formation of granules that actively recruit APC-RNPs, highlighting a new role for Fus in cellular translation within stress-like granules and its relevance to ALS pathology.

Article Abstract

RNA localization pathways direct numerous mRNAs to distinct subcellular regions and affect many physiological processes. In one such pathway the tumor-suppressor protein adenomatous polyposis coli (APC) targets RNAs to cell protrusions, forming APC-containing ribonucleoprotein complexes (APC-RNPs). Here, we show that APC-RNPs associate with the RNA-binding protein Fus/TLS (fused in sarcoma/translocated in liposarcoma). Fus is not required for APC-RNP localization but is required for efficient translation of associated transcripts. Labeling of newly synthesized proteins revealed that Fus promotes translation preferentially within protrusions. Mutations in Fus cause amyotrophic lateral sclerosis (ALS) and the mutant protein forms inclusions that appear to correspond to stress granules. We show that overexpression or mutation of Fus results in formation of granules, which preferentially recruit APC-RNPs. Remarkably, these granules are not translationally silent. Instead, APC-RNP transcripts are translated within cytoplasmic Fus granules. These results unexpectedly show that translation can occur within stress-like granules. Importantly, they identify a new local function for cytoplasmic Fus with implications for ALS pathology.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857475PMC
http://dx.doi.org/10.1083/jcb.201306058DOI Listing

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