ZC3H12A/MCPIP1/Regnase‐1‐related endonucleases: An evolutionary perspective on molecular mechanisms and biological functions

Habacher, Cornelia; Ciosk, Rafal

doi:10.1002/bies.201700051

Cited by 18 publications

(17 citation statements)

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“…In particular, our analysis suggested a new role for ZC3H12, BOLL, and DAZL proteins in regulating alternative splicing and for MEX3B in binding to type I interferonregulated genes. In particular, the binding of the antiviral cytoplasmic ZC3H12 proteins (Lin et al 2013;Habacher and Ciosk 2017) to splice junctions may have a role in their antiviral activity, as endogenous cytoplasmic mRNAs are depleted of splice donor sequences. As a large number of novel motifs were generated in the study, we expect that many other RBPs will have specific roles in particular biological functions.…”

Section: Discussionmentioning

confidence: 99%

Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences

et al. 2020

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“…Recent studies indicate that Regnase-1 plays a broader role in the regulation of RNA beyond immune cells (Skalniak et al, 2014; Boratyn et al, 2016, 2017; Lu et al, 2016). However, phenotypic manifestations clearly show that a major, if not the primary, role of Regnase-1 is within the immune system: namely, preventing autoimmunity and ensuring pathogen defense (Iwasaki et al, 2011; Uehata et al, 2013; Mino and Takeuchi, 2015; Habacher and Ciosk, 2017). Molecular insights have revealed that Regnase-1 is an essential RNase in macrophages and in T cells, where it degrades mRNAs and viral RNAs in the cytoplasm and in foci (called P or GW bodies), which contain other mRNA regulatory factors and mRNAs.…”

Section: Introductionmentioning

confidence: 99%

Immune homeostasis and regulation of the interferon pathway require myeloid-derived Regnase-3

Gamm

Schaub

Jones

et al. 2019

Journal of Experimental Medicine

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The RNase Regnase-1 is a master RNA regulator in macrophages and T cells that degrades cellular and viral RNA upon NF-κB signaling. The roles of its family members, however, remain largely unknown. Here, we analyzed Regnase-3–deficient mice, which develop hypertrophic lymph nodes. We used various mice with immune cell–specific deletions of Regnase-3 to demonstrate that Regnase-3 acts specifically within myeloid cells. Regnase-3 deficiency systemically increased IFN signaling, which increased the proportion of immature B and innate immune cells, and suppressed follicle and germinal center formation. Expression analysis revealed that Regnase-3 and Regnase-1 share protein degradation pathways. Unlike Regnase-1, Regnase-3 expression is high specifically in macrophages and is transcriptionally controlled by IFN signaling. Although direct targets in macrophages remain unknown, Regnase-3 can bind, degrade, and regulate mRNAs, such as Zc3h12a (Regnase-1), in vitro. These data indicate that Regnase-3, like Regnase-1, is an RNase essential for immune homeostasis but has diverged as key regulator in the IFN pathway in macrophages.

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“…In particular, our analysis suggested a new role for ZC3H12, BOLL and DAZL proteins in 506 regulating alternative splicing, and MEX3B in binding to type I interferon-regulated genes. In 507 particular, the binding of the anti-viral cytoplasmic ZC3H12 proteins (Lin et al 2013;Habacher and 508 Ciosk 2017) to splice junctions may have a role in their anti-viral activity, as endogenous cytoplasmic 509 mRNAs are depleted of splice donor sequences. As a large number of novel motifs were generated in 510 the study, we expect that many other RBPs will have specific roles in particular biological functions.…”

mentioning

confidence: 99%

Binding specificities of human RNA binding proteins towards structured and linear RNA sequences

Jolma

Zhang

Mondragón

et al. 2018

Preprint

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of RBPs for which we obtained a motif bound to short linear sequences, whereas 36 ~30% preferred structured motifs folding into stem-loops. We also found that 37 many RBPs can bind to multiple distinctly different motifs. Analysis of the matches 38 of the motifs on human genomic sequences suggested novel roles for many RBPs in 39 regulation of splicing, and revealed RBPs that are likely to control specific classes 40 of transcripts. Global analysis of the motifs also revealed an enrichment of G and U 41 nucleotides. Masking of G and U by proteins increases the specificity of RNA folding, 42 as both G and U can pair to two other RNA bases via canonical Watson-Crick or G-U 43 base pairs. The collection containing 145 high resolution binding specificity 44 models for 86 RBPs is the largest systematic resource for the analysis of human 45RBPs, and will greatly facilitate future analysis of the various biological roles of this 46 important class of proteins. 48All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/317909 doi: bioRxiv preprint first posted online May. 9, 2018; 2 INTRODUCTION 49 50The abundance of protein and RNA molecules in a cell depends both on their rates 51 of production and degradation. These rates are determined directly or indirectly by the 52 sequence of DNA. The transcription rate of RNA and the rate of degradation of proteins is 53 determined by DNA and protein sequences, respectively. However, most regulatory steps 54 that control gene expression are influenced by the sequence of the RNA itself. These 55 processes include RNA splicing, localization, stability, and translation. These processes 56 can be affected by RNA-binding proteins (RBPs) that specifically recognize short RNA 57 sequence elements (Glisovic et al., 2008). 58RBPs can recognize their target sites using two mechanisms: they can form direct 59 contacts to the RNA bases of an unfolded RNA chain, and/or recognise folded RNA-60 structures (Loughlin et al., 2009 256 oligonucleotides, and the desired RBP is then used to select its target sites followed 95 by detection of the bound sites using a second microarray. RNAcompete has been used to 96All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. given protein with 15 amino-acids of flanking sequence (see Table S1 for details). 127Constructs containing subsets of RBDs were also analyzed for some very large RBPs. 128Taken together our clone collection covered 942 distinct proteins. The RBPs were 129 expressed in E.coli as fusion proteins with thioredoxin, incorporating an N-terminal 13...

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ZC3H12A/MCPIP1/Regnase‐1‐related endonucleases: An evolutionary perspective on molecular mechanisms and biological functions

Cited by 18 publications

References 50 publications

Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences

Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences

Immune homeostasis and regulation of the interferon pathway require myeloid-derived Regnase-3

Binding specificities of human RNA binding proteins towards structured and linear RNA sequences

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