Cell Reports
Volume 23, Issue 7, 15 May 2018, Pages 2199-2210
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Article
The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts

https://doi.org/10.1016/j.celrep.2018.04.061Get rights and content
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Highlights

  • Abolished RNA exosome function leads to pA+ RNA accumulation in nuclear foci

  • pA+ RNA foci are enriched with various transcripts and exosome adaptor proteins

  • The exosome adaptor protein ZFC3H1 is required for pA+ RNA foci formation

  • ZFC3H1 functionally counteracts the mRNA export factor AlyREF

Summary

Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci, containing polyadenylated (pA+) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA+ RNA foci with “pA-tail exosome targeting (PAXT) connection” components MTR4, ZFC3H1, and PABPN1 but no overlap with known nuclear structures such as Cajal bodies, speckles, paraspeckles, or nucleoli. Interestingly, ZFC3H1 is required for foci formation, and in its absence, selected pA+ RNAs, including coding and non-coding transcripts, are exported to the cytoplasm in a process dependent on the mRNA export factor AlyREF. Our results establish ZFC3H1 as a central nuclear pA+ RNA retention factor, counteracting nuclear export activity.

Keywords

nuclear RNA decay
nuclear export
nuclear RNA retention
ZFC3H1
AlyREF
RNA exosome
RNA aggregates
MTR4

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Present address: Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen N, Denmark

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