TY - JOUR

T1 - The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts

AU - Silla, Toomas

AU - Karadoulama, Evdoxia

AU - Mąkosa, Dawid

AU - Lubas, Michal

AU - Jensen, Torben Heick

PY - 2018

Y1 - 2018

N2 - 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. Silla et al. report that the RNA exosome adaptor protein ZFC3H1 acts as a nuclear RNA retention factor. In the absence of ZFC3H1, exosome targets are exported to the cytoplasm in a AlyREF-dependent manner. The discovery establishes ZFC3H1 as a central factor in the retention and degradation of polyadenylated RNA.

AB - 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. Silla et al. report that the RNA exosome adaptor protein ZFC3H1 acts as a nuclear RNA retention factor. In the absence of ZFC3H1, exosome targets are exported to the cytoplasm in a AlyREF-dependent manner. The discovery establishes ZFC3H1 as a central factor in the retention and degradation of polyadenylated RNA.

KW - AlyREF

KW - MTR4

KW - nuclear export

KW - nuclear RNA decay

KW - nuclear RNA retention

KW - RNA aggregates

KW - RNA exosome

KW - ZFC3H1

U2 - 10.1016/j.celrep.2018.04.061

DO - 10.1016/j.celrep.2018.04.061

M3 - Journal article

C2 - 29768216

AN - SCOPUS:85046620862

VL - 23

SP - 2199

EP - 2210

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 7

ER -