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
SN - 2211-1247
VL - 23
SP - 2199
EP - 2210
JO - Cell Reports
JF - Cell Reports
IS - 7
ER -