Viperin mRNA is a novel target for the human RNase MRP/RNase P endoribonuclease

Mattijssen, Sandy; Hinson, Ella R.; Onnekink, Carla; Hermanns, Pia; Zabel, Bernhard; Cresswell, Peter; Pruijn, Ger J. M.

doi:10.1007/s00018-010-0568-3

Cited by 31 publications

(34 citation statements)

References 48 publications

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“…Many siRNA and DNA gapmer/antisense oligonucleotide (ASO) reagents failed to affect steady-state MRP RNA abundance, consistent with previous reports (Mattijssen et al 2011). In our hands, only a single siRNA sequence targeting nucleotides 135-154 of MRP RNA achieved modest depletion of MRP RNA by quantitative RT-PCR (qRT-PCR) and RNA fluorescent in situ hybridization (FISH) (Supplemental Fig.…”

Section: Resultssupporting

confidence: 89%

“…(We use the term "MRP/P" to indicate the mixture of these two RNPs, which copurify because of their shared protein components.) Others (Welting et al 2006;Mattijssen et al 2011) have shown that N-terminal tags on MRP/P protein components enable immunopurification of pre-tRNA cleavage activity from human cells. Building on these observations and in response to ineffective isolation of RNase MRP via tagging the MRP RNA (data not shown), we constructed 3xFlag-Rpp25 and 3xFlag-Rpp38 for transfection in HeLa cells (see the Supplemental Material).…”

Section: Immunopurified Human Mrp Rnp Specifically Cleaves Fragments mentioning

confidence: 99%

“…Alternative roles for MRP RNA have been described in yeast and human cells (Chang and Clayton 1987;Gill et al 2006;Jaag et al 2011;Mattijssen et al 2011;Huang et al 2015), and many of these functions are undoubtedly important for their specific niches (e.g., T lymphocytes). However, these functions are not essential in all cell types that abundantly express MRP RNA.…”

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confidence: 99%

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Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing

2017

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MRP RNA is an abundant, essential noncoding RNA whose functions have been proposed in yeast but are incompletely understood in humans. Mutations in the genomic locus for MRP RNA cause pleiotropic human diseases, including cartilage hair hypoplasia (CHH). Here we applied CRISPR-Cas9 genome editing to disrupt the endogenous human MRP RNA locus, thereby attaining what has eluded RNAi and RNase H experiments: elimination of MRP RNA in the majority of cells. The resulting accumulation of ribosomal RNA (rRNA) precursor-analyzed by RNA fluorescent in situ hybridization (FISH), Northern blots, and RNA sequencing-implicates MRP RNA in pre-rRNA processing. Amelioration of pre-rRNA imbalance is achieved through rescue of MRP RNA levels by ectopic expression. Furthermore, affinity-purified MRP ribonucleoprotein (RNP) from HeLa cells cleaves the human pre-rRNA in vitro at at least one site used in cells, while RNP isolated from cells with CRISPR-edited MRP loci loses this activity, and ectopic MRP RNA expression restores cleavage activity. Thus, a role for RNase MRP in human pre-rRNA processing is established. As demonstrated here, targeted CRISPR disruption is a valuable tool for functional studies of essential noncoding RNAs that are resistant to RNAi and RNase H-based degradation.

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Section: Resultssupporting

confidence: 89%

Section: Immunopurified Human Mrp Rnp Specifically Cleaves Fragments mentioning

confidence: 99%

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confidence: 99%

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Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing

2017

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“…Pop1 mutations affect the holoenzyme assembly and result in destabilization of the RNA component in the cell as well as in substrate processing defects in both RNase P and RNase MRP (Lygerou et al 1994;Chamberlain et al 1998;Xiao et al 2006). In humans, certain Pop1 mutations result in a severe skeletal dysplasia (Glazov et al 2011), similar to the dysplasias caused by mutations in the RNase MRP RNA or by defects in RNase MRP RNA promoter region (Ridanpaa et al 2001;Mattijssen et al 2011). …”

Section: Introductionmentioning

confidence: 99%

Footprinting analysis of interactions between the largest eukaryotic RNase P/MRP protein Pop1 and RNase P/MRP RNA components

Fagerlund

Perederina

Berezin

et al. 2015

RNA

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Ribonuclease (RNase) P and RNase MRP are closely related catalytic ribonucleoproteins involved in the metabolism of a wide range of RNA molecules, including tRNA, rRNA, and some mRNAs. The catalytic RNA component of eukaryotic RNase P retains the core elements of the bacterial RNase P ribozyme; however, the peripheral RNA elements responsible for the stabilization of the global architecture are largely absent in the eukaryotic enzyme. At the same time, the protein makeup of eukaryotic RNase P is considerably more complex than that of the bacterial RNase P. RNase MRP, an essential and ubiquitous eukaryotic enzyme, has a structural organization resembling that of eukaryotic RNase P, and the two enzymes share most of their protein components. Here, we present the results of the analysis of interactions between the largest protein component of yeast RNases P/MRP, Pop1, and the RNA moieties of the enzymes, discuss structural implications of the results, and suggest that Pop1 plays the role of a scaffold for the stabilization of the global architecture of eukaryotic RNase P RNA, substituting for the network of RNA-RNA tertiary interactions that maintain the global RNA structure in bacterial RNase P.

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“…It was reported that viperin was a target of human RNase endoribonuclease (33) and that UL41 was an endoribonuclease with a substrate specificity similar to that of RNase A (26). Therefore, it is very likely that UL41 abolishes viperin expression via its RNase activity to degrade viperin mRNA.…”

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confidence: 99%

Herpes Simplex Virus 1 Counteracts Viperin via Its Virion Host Shutoff Protein UL41

Shen

Wang

et al. 2014

J Virol

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bThe interferon (IFN)-inducible viperin protein restricts a broad range of viruses. However, whether viperin plays a role during herpes simplex virus 1 (HSV-1) infection is poorly understood. In the present study, it was shown for the first time that wild-type (WT) HSV-1 infection couldn't induce viperin production, and ectopically expressed viperin inhibited the replication of UL41-null HSV-1 but not WT viruses. The underlying molecular mechanism is that UL41 counteracts viperin's antiviral activity by reducing its mRNA accumulation. Viperin is a highly conserved, 361-amino-acid protein. It was first identified as a gamma interferon (IFN-␥)-inducible protein which is directly induced by human cytomegalovirus (HCMV), and its constitutive expression is low (1). The viperin gene (also known as cig5 or RASD2) can also be categorized as an antiviral interferon-stimulated gene (ISG) which limits the replication of many DNA and RNA viruses (1-14). However, whether viperin plays a role during herpes simplex virus 1 (HSV-1) infection is unknown.To investigate whether HSV-1 could induce the expression of viperin, HEK293T cells were infected with wild-type (WT) HSV-1 at different multiplicities of infection (MOI) or with Sendai virus (SeV) (15). Infection with SeV induced a significant amount of viperin; however, infection with a low MOI (0.2) of HSV-1 induced only a trace amount of viperin, and infection with a moderate MOI (2) abrogated the expression of viperin (Fig. 1A).To further explore whether viperin could inhibit the replication of WT HSV-1, HEK293T cells with ectopic expression of viperin-Flag were infected with HSV-1 at an MOI of 0.2. Then cells were harvested at the time points indicated in the figures, and viral plaque assay was performed to determine viral replication (16). As a result, ectopically expressed viperin did not affect the replication of WT HSV-1 (Fig. 1B). The data from Western blot (WB) analysis also showed that viperin did not affect viral protein expression (Fig. 1C). These results demonstrated that ectopic expression of viperin failed to inhibit the replication of WT HSV-1.The aforementioned data led us to hypothesize that at least one of the HSV-1 proteins could counteract the expression of viperin. As a member of the ISGs, viperin was effectively induced by SeV ( Fig. 1) (15). With a high-throughput screen assay of all 84 proteins carried by HSV-1, dual-luciferase reporter gene assays were performed in HEK293T cells cotransfected with viperin-luciferase reporter plasmid and individual HSV-1 protein expression plasmid for 20 h and infected with SeV (17). As a result, ectopically expressed UL41 abrogated the expression of viperin; however, other HSV-1 proteins did not (data not shown). UL41 has been reported to degrade both viral and cellular mRNAs (18)(19)(20)(21)(22)(23)(24)(25)(26). Recently, mRNA of tetherin has been reported to be degraded by UL41 (27). Meanwhile, ICP0, an E3 ubiquitin ligase, promotes degradation of many cellular antiviral proteins, such as IRF3, IRF7, IFI16, and ATRX ...

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Viperin mRNA is a novel target for the human RNase MRP/RNase P endoribonuclease

Cited by 31 publications

References 48 publications

Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing

Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing

Footprinting analysis of interactions between the largest eukaryotic RNase P/MRP protein Pop1 and RNase P/MRP RNA components

Herpes Simplex Virus 1 Counteracts Viperin via Its Virion Host Shutoff Protein UL41

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