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The human ZC3H3 and RBM26/27 proteins are critical for PAXT-mediated nuclear RNA decay

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Item Type:Article
Title:The human ZC3H3 and RBM26/27 proteins are critical for PAXT-mediated nuclear RNA decay
Creators Name:Silla, T., Schmid, M., Dou, Y., Garland, W., Milek, M., Imami, K., Johnsen, D., Polak, P., Andersen, J.S., Selbach, M., Landthaler, M. and Jensen, T.
Abstract:Recruitment of the human ribonucleolytic RNA exosome to nuclear polyadenylated (pA(+)) RNA is facilitated by the Poly(A) Tail eXosome Targeting (PAXT) connection. Besides its core dimer, formed by the exosome co-factor MTR4 and the ZFC3H1 protein, the PAXT connection remains poorly defined. By characterizing nuclear pA(+)-RNA bound proteomes as well as MTR4-ZFC3H1 containing complexes in conditions favoring PAXT assembly, we here uncover three additional proteins required for PAXT function: ZC3H3, RBM26 and RBM27 along with the known PAXT-associated protein, PABPN1. The zinc-finger protein ZC3H3 interacts directly with MTR4-ZFC3H1 and loss of any of the newly identified PAXT components results in the accumulation of PAXT substrates. Collectively, our results establish new factors involved in the turnover of nuclear pA(+) RNA and suggest that these are limiting for PAXT activity.
Keywords:Exosomes, HEK293 Cells, HeLa Cells, Nuclear RNA, Poly A, Protein Binding, Proteome, RNA Stability, RNA-Binding Proteins, Ribonucleoproteins
Source:Nucleic Acids Research
ISSN:0305-1048
Publisher:Oxford University Press
Volume:48
Number:5
Page Range:2518-2530
Date:18 March 2020
Official Publication:https://doi.org/10.1093/nar/gkz1238
PubMed:View item in PubMed

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