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
Mar 8, 2019·Genes & Development·Jianshu WangHong Cheng
Sep 26, 2019·RNA·Carmen AdriaensJean-Christophe Marine
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 20, 2018·Scientific Reports·Joseph RussoCarol J Wilusz
Jul 31, 2019·Nature Communications·Mahesh LingarajuElena Conti
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
Feb 6, 2020·PLoS Genetics·Yuichi ShichinoAkira Yamashita
Jan 9, 2020·The Biochemical Journal·Asaf Ashkenazy-TitelmanRalph H Kehlenbach
Jul 28, 2020·Nucleic Acids Research·Mengjun WuAlbin Sandelin
Nov 14, 2019·Cell Reports·William GarlandTorben Heick Jensen
Apr 25, 2021·Experimental Eye Research·Ales Cvekl, Carolina Eliscovich
May 29, 2021·Cancer Cell·Yuanming ChengMichael G Kharas
Jun 7, 2020·Molecular Cell·Binyamin ZuckermanIgor Ulitsky
Sep 3, 2021·RNA Biology·Tanzina TanuNobuyoshi Akimitsu
Sep 14, 2021·Bioengineered·Hang HuangXixi Huang
Sep 17, 2021·Nucleic Acids Research·Yimin WangHong Cheng
Dec 27, 2021·The Plant Cell·Heike Lange, Dominique Gagliardi