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Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609 /CKAP5 mRNA interaction might have a potent output in tumor growth and drug response. [Display omitted] • circZNF609 interacts with CKAP5 , UPF2 , and SRRM1 mRNAs in vivo • circZNF609-mRNA interaction increases ELAVL1 loading on the mRNAs • ELAVL1 loading by circZNF609 regulates stability and translation of its targets • CAKP5 regulation alters MT dynamics, sensitizing cells to chemotherapeutic drugs In this article, Rossi et al. provide an interesting mechanism in which circZNF609-mRNA interaction increases translation, and among them, CKAP5 is a key factor in microtubule dynamics stability. The authors show how the disruption of RNA-RNA interactions is able to alter microtubule dynamics, sensitizing rhabdomyosarcoma cells to chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]

A number of regulatory factors are recruited to chromatin by specialized RNAs. Whether RNA has a more general role in regulating the interaction of proteins with chromatin has not been determined. We used proteomics methods to measure the global impact of nascent RNA on chromatin in embryonic stem cells. Surprisingly, we found that nascent RNA primarily antagonized the interaction of chromatin modifiers and transcriptional regulators with chromatin. Transcriptional inhibition and RNA degradation induced recruitment of a set of transcriptional regulators, chromatin modifiers, nucleosome remodelers, and regulators of higher-order structure. RNA directly bound to factors, including BAF, NuRD, EHMT1, and INO80 and inhibited their interaction with nucleosomes. The transcriptional elongation factor P-TEFb directly bound pre-mRNA, and its recruitment to chromatin upon Pol II inhibition was regulated by the 7SK ribonucleoprotein complex. We postulate that by antagonizing the interaction of regulatory proteins with chromatin, nascent RNA links transcriptional output with chromatin composition. [Display omitted] • Pol II inhibition induced recruitment of a set of regulatory proteins to chromatin • Many of these changes were also observed upon RNA degradation • RNA binds a set of chromatin modifiers and inhibits interaction with nucleosomes • P-TEFb binds pre-mRNA, and 7SK regulates its interaction with RNA and chromatin Nascent RNA interacts with a wide array of regulatory proteins but its impact on chromatin composition has not been assessed. Skalska and colleagues use proteomics methods to reveal that nascent RNA antagonizes the association of a set of regulatory proteins with chromatin. [ABSTRACT FROM AUTHOR]

Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain gene repression and is essential for cell differentiation. In low-grade endometrial stromal sarcoma (LG-ESS), the PRC2 subunit SUZ12 is often fused with the NuA4/TIP60 subunit JAZF1. We show that JAZF1-SUZ12 dysregulates PRC2 composition, genome occupancy, histone modification, gene expression, and cell differentiation. Loss of the SUZ12 N terminus in the fusion protein abrogates interaction with specific PRC2 accessory factors, reduces occupancy at PRC2 target genes, and diminishes H3K27me3. Fusion to JAZF1 increases H4Kac at PRC2 target genes and triggers recruitment to JAZF1 binding sites during cell differentiation. In human endometrial stromal cells, JAZF1-SUZ12 upregulated PRC2 target genes normally activated during decidualization while repressing genes associated with immune clearance, and JAZF1-SUZ12-induced genes were also overexpressed in LG-ESS. These results reveal defects in chromatin regulation, gene expression, and cell differentiation caused by JAZF1-SUZ12 that may underlie its role in oncogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)