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

Published

Journal Article

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 APCcontaining ribonucleoprotein complexes (APC-RNPs). Here, we show that APC-RNPs associate with the RNAbinding 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.

Full Text

Duke Authors

Cited Authors

  • Yasuda, K; Zhang, H; Loiselle, D; Haystead, T; Macara, IG; Mili, S

Published Date

  • December 9, 2013

Published In

Volume / Issue

  • 203 / 5

Start / End Page

  • 737 - 746

Electronic International Standard Serial Number (EISSN)

  • 1540-8140

International Standard Serial Number (ISSN)

  • 0021-9525

Digital Object Identifier (DOI)

  • 10.1083/jcb.201306058

Citation Source

  • Scopus