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

Cell Reports
Toomas SillaTorben Heick Jensen

Abstract

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.

Citations

Mar 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Ke WangHong Cheng
Jan 18, 2020·Nucleic Acids Research·Toomas SillaTorben Heick Jensen
May 29, 2020·Nucleic Acids Research·Mireille MelkoTorben Heick Jensen
May 30, 2020·International Journal of Molecular Sciences·Hui ZhangCheng-Jun Hu
Jun 11, 2020·Cold Spring Harbor Symposia on Quantitative Biology·Chao DiGideon Dreyfuss
Sep 5, 2020·Essays in Biochemistry·Jianshu Wang, Hong Cheng
Sep 23, 2020·Nucleic Acids Research·Yuhui DouTorben Heick Jensen
Nov 13, 2019·Wiley Interdisciplinary Reviews. RNA·William Garland, Torben Heick Jensen
Nov 24, 2019·The Journal of Cell Biology·Jiah KimAndrew S Belmont
Feb 6, 2020·Nature Reviews. Molecular Cell Biology·Lekha NairUttiya Basu
Jun 21, 2020·Nature Communications·Clémentine Delan-ForinoDavid Tollervey
Dec 6, 2018·Current Genetics·Agnieszka TudekTorben Heick Jensen
Jan 9, 2020·The Biochemical Journal·Asaf Ashkenazy-TitelmanRalph H Kehlenbach
Jul 28, 2020·Nucleic Acids Research·Mengjun WuAlbin Sandelin
Apr 25, 2021·Experimental Eye Research·Ales Cvekl, Carolina Eliscovich
Sep 17, 2021·Nucleic Acids Research·Yimin WangHong Cheng

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Methods Mentioned

BETA
RNA-seq
transfection
transfections
smiFISH

Software Mentioned

PONDR
Fiji
R Project for
R script Oligostan
DESeq2
FIT

Related Concepts

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Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.

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