Characterizing ZC3H18, a Multi-domain Protein at the Interface of RNA Production and Destruction Decisions

Winczura, Kinga; Schmid, Manfred; Iasillo, Claudia; Molloy, Kelly R.; Harder, Lea Mørch; Andersen, Jens S.; LaCava, John; Jensen, Torben Heick

doi:10.1016/j.celrep.2017.12.037

Cited by 46 publications

(47 citation statements)

References 43 publications

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“…The EMBO GTF3C3,GTF3C4,GTF3C5 TXLNA,TNPO1,MAP3K20,PRPF19 CALU,RCN2,HNRNPH1,GANAB WDR62,HIST1H1C,NUMA1,SNRPD2 CCT4, CCT5, CCT8, TCP1 COPG1,COPA,RPS27A CCNA2,CDK2,CDK1 ZNF460,ZNF677,c18orf25 RNH1,SART3, these KZFPs, while perhaps still repressing transcription, do so no longer to block retrotransposition, since their target retroelements have long lost all spreading potential. ZNF765 is recruited over the L1PA5/PA6 promoter region, and two of its interactors stand out as potential regulators of LINE1 transcripts: the RNA-binding proteins interactor ZKSCAN4 and ZC3H18, known to be involved in RNA export, anabolism, and catabolism (Chi et al, 2014;Winczura et al, 2018). Furthermore, L1PA6 and L1PA5 integrants also recruit over their 3 0 half two KZFPs with conventional KAP1-centered interactomes, ZNF382 and ZNF84, for which there is no sign of mutational escape, strongly suggesting that these KZFPs, in spite of their repressor potential, never limited the spread of these retrotransposons.…”

Section: Of 16mentioning

confidence: 99%

The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification

et al. 2019

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Krüppel‐associated box (KRAB)‐containing zinc finger proteins (KZFPs) are encoded in the hundreds by the genomes of higher vertebrates, and many act with the heterochromatin‐inducing KAP1 as repressors of transposable elements (TEs) during early embryogenesis. Yet, their widespread expression in adult tissues and enrichment at other genetic loci indicate additional roles. Here, we characterized the protein interactome of 101 of the ~350 human KZFPs. Consistent with their targeting of TEs, most KZFPs conserved up to placental mammals essentially recruit KAP1 and associated effectors. In contrast, a subset of more ancient KZFPs rather interacts with factors related to functions such as genome architecture or RNA processing. Nevertheless, KZFPs from coelacanth, our most distant KZFP‐encoding relative, bind the cognate KAP1. These results support a hypothetical model whereby KZFPs first emerged as TE‐controlling repressors, were continuously renewed by turnover of their hosts’ TE loads, and occasionally produced derivatives that escaped this evolutionary flushing by development and exaptation of novel functions.

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Section: Of 16mentioning

confidence: 99%

The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification

et al. 2019

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“…Finally, RNA association of the exosome factors proposed to interact with poly(A) tail such as Pab2 and Red5 is decreased in exosome mutants ( Figure 8D) suggesting that exosome either directly or indirectly contributes to assembly of these factors with RNA. and ZFC3H1 supporting an evolutionary conserved role for these proteins in exosome regulation (80)(81)(82). ZCCHC8 interacts with RNA binding protein RMB7 and helicase MTR4 to form the trimeric Nuclear EXosome Targeting (NEXT) (81,83).…”

Section: Mub1 Regulates Exosome Degradation Of the Stress-induced Mrnasmentioning

confidence: 92%

RNA-binding protein Mub1 and the nuclear RNA exosome act to fine-tune environmental stress response

Birot

Kilchert

Kuś

et al. 2020

Preprint

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ABSTRACTThe nuclear RNA exosome plays a key role in quality control and processing of multiple protein-coding and non-coding transcripts made by RNA polymerase II. A mechanistic understanding of exosome function remains a challenge given it has multiple roles in RNA regulation. Here we have analysed changes in the poly(A)+ RNA transcriptome and interactome provoked by mutations in three distinct subunits of the nuclear RNA exosome. We have identified multiple proteins whose occupancy on RNA is altered in the exosome mutants. We demonstrate that the Zinc-finger protein Mub1 regulates exosome dependent transcripts that encode stress-responsive proteins. Furthermore, we assess impact of the exosome inactivation upon RNA binding of the components of the mRNA processing machineries such as spliceosome and mRNA cleavage polyadenylation complex. We show that mutations in the exosome lead to accumulation of the components of U1 and U2 snRNPs on poly(A)+ RNA and depletion of the components of the activated spliceosome from RNA suggesting that the early stages of spliceosome assembly might provide a critical quality control step. Collectively, our data provide a global view of how RNA metabolism is affected in the exosome-deficient cells and reveal RNA-binding proteins that may act as novel exosome cofactors.

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“…5b). Employing RNA-seq data collected in parallel (53,54) demonstrated that NCBP1 depletion did not show such an exon-content effect on RNA levels (Fig. 5d, Supplementary Fig.…”

Section: Ncbp3 Depletion Causes Exon-number Biased Regulation Of Rna mentioning

confidence: 98%

“…RNA extraction and RNA-seq library preparation upon GFP and NCBP3 depletion were performed as described (53). Total RNAseq of siNCBP3 depletion samples are first reported here, but were collected as part of same experiment described in (53,54).…”

Section: Rna Sequencing (Rna-seq) and Data Analysismentioning

confidence: 99%

NCBP3 is a productive mRNP component

Dou

Barbosa

Jiang

et al. 2020

Preprint

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AbstractThe nuclear Cap Binding Complex (CBC), consisting of Nuclear Cap Binding Protein 1 (NCBP1) and 2 (NCBP2), associates with the nascent 5’cap of RNA polymerase II transcripts and impacts RNA fate decisions. Recently, the C17orf85 protein, also called NCBP3, was suggested to form an alternative CBC by replacing NCBP2. However, applying protein-protein interaction screening of NCBP1, 2 and 3, we find that the interaction profile of NCBP3 is distinct. Whereas NCBP1 and 2 identify known CBC interactors, NCBP3 primarily interacts with components of the Exon Junction Complex (EJC) and the TRanscription and EXport (TREX) complex. NCBP3-EJC association in vitro and in vivo requires EJC core integrity and the in vivo RNA binding profiles of EJC and NCBP3 overlap. We further show that NCBP3 competes with the RNA degradation factor ZC3H18 for binding CBC-bound transcripts, and that NCBP3 positively impacts the nuclear export of polyadenylated RNAs and the expression of large multi-exonic transcripts. Collectively, our results place NCBP3 with the EJC and TREX complexes in supporting the productive fate of mRNA.

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Characterizing ZC3H18, a Multi-domain Protein at the Interface of RNA Production and Destruction Decisions

Cited by 46 publications

References 43 publications

The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification

The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification

RNA-binding protein Mub1 and the nuclear RNA exosome act to fine-tune environmental stress response

NCBP3 is a productive mRNP component

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