Defects in THO/TREX-2 function cause accumulation of novel cytoplasmic mRNP granules that can be cleared by autophagy
AffiliationUniv Arizona, Dept Mol & Cellular Biol
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CitationEshleman, N., Liu, G., McGrath, K., Parker, R., & Buchan, J. R. (2016). Defects in THO/TREX-2 function cause accumulation of novel cytoplasmic mRNP granules that can be cleared by autophagy. Rna, 22(8), 1200-1214.
RightsCopyright © 2016 Eshleman et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society. This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
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AbstractThe nuclear THO and TREX-2 complexes are implicated in several steps of nuclear mRNP biogenesis, including transcription, 3′ end processing and export. In a recent genomic microscopy screen in Saccharomyces cerevisiae for mutants with constitutive stress granules, we identified that absence of THO and TREX-2 complex subunits leads to the accumulation of Pab1-GFP in cytoplasmic foci. We now show that these THO/TREX-2 mutant induced foci (“TT foci”) are not stress granules but instead are a mRNP granule containing poly(A)+ mRNA, some mRNP components also found in stress granules, as well several proteins involved in mRNA 3′ end processing and export not normally seen in stress granules. In addition, TT foci are resistant to cycloheximide-induced disassembly, suggesting the presence of mRNPs impaired for entry into translation. THO mutants also exhibit defects in normal stress granule assembly. Finally, our data also suggest that TT foci are targeted by autophagy. These observations argue that defects in nuclear THO and TREX-2 complexes can affect cytoplasmic mRNP function by producing aberrant mRNPs that are exported to cytosol, where they accumulate in TT foci and ultimately can be cleared by autophagy. This identifies a novel mechanism of quality control for aberrant mRNPs assembled in the nucleus.
Note12 month embargo; published online: 1 June 2016
VersionFinal published version
SponsorsHoward Hughes Medical Institute; University of Arizona
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