Xenopus U8 snoRNA Binding Protein Is a Conserved Nuclear Decapping Enzyme

Ghosh, Trina; Peterson, Brian; Tomašević, Nenad; Peculis, Brenda A.

doi:10.1016/s1097-2765(04)00127-3

Cited by 61 publications

(99 citation statements)

References 47 publications

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“…Consistent with a previous report, Nudt16 hydrolyzed the GpppRNA unmethylated capped RNA and generated GMP decapping product ( Fig. 1C; Ghosh et al 2004). Unexpectedly, Dcp2 could also hydrolyze GpppRNA and released GDP.…”

Section: Identification Of Mammalian Nudix Proteins Possessing Decappsupporting

confidence: 92%

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Multiple Nudix family proteins possess mRNA decapping activity

Song

Bail

Kiledjian

2013

RNA

120

139

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RNA decapping is an important contributor to gene expression and is a critical determinant of mRNA decay. The recent demonstration that mammalian cells harbor at least two distinct decapping enzymes that preferentially modulate a subset of mRNAs raises the intriguing possibility of whether additional decapping enzymes exist. Because both known decapping proteins, Dcp2 and Nudt16, are members of the Nudix hydrolase family, we set out to determine whether other members of this family of proteins also contain intrinsic RNA decapping activity. Here we demonstrate that six additional mouse Nudix proteins-Nudt2, Nudt3, Nudt12, Nudt15, Nudt17, and Nudt19-have varying degrees of decapping activity in vitro on both monomethylated and unmethylated capped RNAs. The decapping products from Nudt17 and Nudt19 were analogous to Dcp2 and predominantly generated m 7 GDP, while cleavage by Nudt2, Nudt3, Nudt12, and Nudt15 was more pleiotropic and generated both m 7 GMP and m 7 GDP. Interestingly, all six Nudix proteins as well as both Dcp2 and Nudt16 could hydrolyze the cap of an unmethylated capped RNA, indicating that decapping enzymes may be less constrained for the presence of the methyl moiety. Investigation of Saccharomyces cerevisiae Nudix proteins revealed that the yeast homolog of Nudt3, Ddp1p, also possesses decapping activity in vitro. Moreover, the bacterial Nudix pyrophosphohydrolase RppH displayed RNA decapping activity and released m 7 GDP product comparable to Dcp2, indicating that decapping is an evolutionarily conserved activity that preceded mammalian cap formation. These findings demonstrate that multiple Nudix family hydrolases may function in mRNA decapping and mRNA stability.

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Section: Identification Of Mammalian Nudix Proteins Possessing Decappsupporting

confidence: 92%

“…Nudt16 was initially identified in Xenopus as a nucleolar decapping enzyme that specifically binds the U8 snoRNA (Tomasevic and Peculis 1999;Ghosh et al 2004). It was subsequently shown to be a cytoplasmic protein in mammalian cells and involved in mRNA decapping (Song et al 2010).…”

Section: Eukaryotic Mrnas Are Modified With Amentioning

confidence: 99%

Multiple Nudix family proteins possess mRNA decapping activity

Song

Bail

Kiledjian

2013

RNA

120

139

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“…The recent demonstrations that both Dcp2 and Nudt16 possess transcript-specific decapping properties (Ghosh et al 2004;Li et al 2008Li et al , 2009) prompted us to test whether various mRNA decay processes differentially utilized the two decapping enzymes and assessed their roles in nonsense-mediated decay (NMD), ARE-mediated decay, and noncoding RNA-mediated gene silencing. The effect of Dcp2 on the reduction of nonsense mRNA levels was assessed by transiently transfecting MEF cells with plasmids encoding either a normal b-globin transcript lacking a nonsense mutation (Norm) or its nonsense mutation-containing version (PTC39).…”

Section: Preferential Utilization Of Dcp2 In Nmdmentioning

confidence: 99%

“…The X29 protein was first identified in Xenopus as a nuclear decapping protein that specifically binds U8 snoRNA (Tomasevic and Peculis 1999;Ghosh et al 2004). However, we recently demonstrated that the mammalian homolog, Nudt16, is a cytoplasmic decapping enzyme and can regulate the stability of specific mRNA substrates (Song et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Differential utilization of decapping enzymes in mammalian mRNA decay pathways

Li¹,

Song²,

Kiledjian³

2011

RNA

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mRNA decapping is a crucial step in the regulation of mRNA stability and gene expression. Dcp2 is an mRNA decapping enzyme that has been widely studied. We recently reported the presence of a second mammalian cytoplasmic decapping enzyme, Nudt16. Here we address the differential utilization of the two decapping enzymes in specified mRNA decay processes. Using mouse embryonic fibroblast (MEF) cell lines derived from a hypomorphic knockout of the Dcp2 gene with undetectable levels of Dcp2 or MEF cell lines harboring a Nudt16-directed shRNA to generate reduced levels of Nudt16, we demonstrate the distinct roles for Dcp2 and Nudt16 in nonsense-mediated mRNA decay (NMD), decay of ARE-containing mRNA and miRNA-mediated silencing. Our results indicated that NMD preferentially utilizes Dcp2 rather than Nudt16; Dcp2 and Nudt16 are redundant in miRNA-mediated silencing; and Dcp2 and Nudt16 are differentially utilized for ARE-mRNA decay. These data demonstrate that the two distinct decapping enzymes can uniquely function in specific mRNA decay processes in mammalian cells.

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“…Finally, the nuclear decay of pre-mRNAs and nuclear-restricted mRNAs also seems to involve decapping of such transcripts (Kufel et al 2004). A nuclear protein with decapping activity, Nudt16/X29, is conserved in several organisms (Taylor and Peculis 2008) and has the ability to cleave both m 7 -monomethyl and m 2,2,7 -trimethyl caps (characteristic of snRNAs and snoRNAs) of RNAs in vitro (Ghosh et al 2004), implying that decapping may be a required step in the decay of several different RNA substrates in the nucleus.…”

Section: Introductionmentioning

confidence: 99%

Activation of decapping involves binding of the mRNA and facilitation of the post-binding steps by the Lsm1-7–Pat1 complex

Chowdhury¹,

Tharun²

2009

RNA

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Decapping is a critical step in the conserved 59-to-39 mRNA decay pathway of eukaryotes. The hetero-octameric Lsm1-7-Pat1 complex is required for normal rates of decapping in this pathway. This complex also protects the mRNA 39-ends from trimming in vivo. To elucidate the mechanism of decapping, we analyzed multiple lsm1 mutants, lsm1-6, lsm1-8, lsm1-9, and lsm1-14, all of which are defective in decapping and 39-end protection but unaffected in Lsm1-7-Pat1 complex integrity. The RNA binding ability of the mutant complex was found to be almost completely lost in the lsm1-8 mutant but only partially impaired in the other mutants. Importantly, overproduction of the Lsm1-9p-or Lsm1-14p-containing (but not Lsm1-8p-containing) mutant complexes in wild-type cells led to a dominant inhibition of mRNA decay. Further, the mRNA 39-end protection defect of lsm1-9 and lsm1-14 cells, but not the lsm1-8 cells, could be partly suppressed by overproduction of the corresponding mutant complexes in those cells. These results suggest the following: (1) Decapping requires both binding of the Lsm1-7-Pat1 complex to the mRNA and facilitation of the post-binding events, while binding per se is sufficient for 39-end protection. (2) A major block exists at the post-binding steps in the lsm1-9 and lsm1-14 mutants and at the binding step in the lsm1-8 mutant. Consistent with these ideas, the lsm1-9, 14 allele generated by combining the mutations of lsm1-9 and lsm1-14 alleles had almost fully lost the RNA binding activity of the complex and behaved like the lsm1-8 mutant.

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Xenopus U8 snoRNA Binding Protein Is a Conserved Nuclear Decapping Enzyme

Cited by 61 publications

References 47 publications

Multiple Nudix family proteins possess mRNA decapping activity

Multiple Nudix family proteins possess mRNA decapping activity

Differential utilization of decapping enzymes in mammalian mRNA decay pathways

Activation of decapping involves binding of the mRNA and facilitation of the post-binding steps by the Lsm1-7–Pat1 complex

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