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

Toomas Silla, Manfred Schmid, Yuhui Dou, William Garland, Miha Milek, Koshi Imami, Dennis Johnsen, Patrik Polak, Jens S. Andersen, Matthias Selbach, Markus Landthaler, Torben Heick Jensen*

*Corresponding author for this work

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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.

Original languageEnglish
JournalNucleic acids research
Volume48
Issue number5
Pages (from-to)2518-2530
Number of pages13
ISSN0305-1048
DOIs
Publication statusPublished - 18. Mar 2020

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    Silla, T., Schmid, M., Dou, Y., Garland, W., Milek, M., Imami, K., Johnsen, D., Polak, P., Andersen, J. S., Selbach, M., Landthaler, M., & Jensen, T. H. (2020). The human ZC3H3 and RBM26/27 proteins are critical for PAXT-mediated nuclear RNA decay. Nucleic acids research, 48(5), 2518-2530. https://doi.org/10.1093/nar/gkz1238