Dxo1 is a new type of eukaryotic enzyme with both decapping and 5′-3′ exoribonuclease activity

Chang, Jeong Ho; Jiao, Xuan; Chiba, Kunitoshi; Oh, Chan-Seok; Martin, Charles E.; Kiledjian, Megerditch; Tong, Liang

doi:10.1038/nsmb.2381

Cited by 95 publications

(164 citation statements)

References 43 publications

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“…Multiple Nudix family members can decap mRNA in vitro and likely in cells, and experiments are under way to determine the latter. The recent demonstration that the yeast Rai1 (Xiang et al 2009;Jiao et al 2010) and Dxo1 (Chang et al 2012) proteins, which are not members of the Nudix family of hydrolases, also contain decapping activity that preferentially functions on incompletely capped mRNAs, strongly suggests that there may yet be additional uncharacterized decapping proteins that modulate mRNA decay in cells. Furthermore, the surprising ability of all the decapping-competent Nudt proteins to also function on unmethylated capped RNAs to varying degrees raises an interesting question of whether these proteins may also function on incompletely capped mRNAs in cells and how they may be regulated.…”

Section: Discussionmentioning

confidence: 99%

“…Having recently demonstrated that a subclass of decapping enzymes preferentially functions on incompletely capped mRNAs lacking the N7 methyl moiety (Jiao et al 2010;Chang et al 2012), we tested the capacity of the Nudix proteins to decap unmethylated capped RNA. Consistent with a previous report, Nudt16 hydrolyzed the GpppRNA unmethylated capped RNA and generated GMP decapping product ( Fig.…”

Section: Identification Of Mammalian Nudix Proteins Possessing Decappmentioning

confidence: 99%

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Multiple Nudix family proteins possess mRNA decapping activity

Song

Bail

Kiledjian

2013

RNA

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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: Discussionmentioning

confidence: 99%

Section: Identification Of Mammalian Nudix Proteins Possessing Decappmentioning

confidence: 99%

Multiple Nudix family proteins possess mRNA decapping activity

Song

Bail

Kiledjian

2013

RNA

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120

139

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“…tRNA intron turnover-healing and decay and Dxo1, which is primarily cytoplasmic (Chang et al 2012), were examined. There is no accumulation of tRNA introns in RNAs from dxo1D or rai1D cells (Fig.…”

Section: The Trna Ligase Rlg1 Phosphorylates Trna Introns Prior To Dementioning

confidence: 99%

Healing for destruction: tRNA intron degradation in yeast is a two-step cytoplasmic process catalyzed by tRNA ligase Rlg1 and 5′-to-3′ exonuclease Xrn1

Hopper

2014

Genes Dev.

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In eukaryotes and archaea, tRNA splicing generates free intron molecules. Although~600,000 introns are produced per generation in yeast, they are barely detectable in cells, indicating efficient turnover of introns. Through a genome-wide search for genes involved in tRNA biology in yeast, we uncovered the mechanism for intron turnover. This process requires healing of the 59 termini of linear introns by the tRNA ligase Rlg1 and destruction by the cytoplasmic tRNA quality control 59-to-39 exonuclease Xrn1, which has specificity for RNAs with 59 monophosphate.

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“…[55][56][57] Although the efficiency of silencing was very high for both proteins (Fig. S11A, D), similarly to hXRN2 downregulation we did not observe any changes in the pattern of processing at site A 1 upon hUTP24 dysfunction (Fig.…”

mentioning

confidence: 99%

hUTP24 is essential for processing of the human rRNA precursor at site A₁, but not at site A₀

et al. 2015

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Production of ribosomes relies on more than 200 accessory factors to ensure the proper sequence of steps and faultless assembly of ribonucleoprotein machinery. Among trans-acting factors are numerous enzymes, including ribonucleases responsible for processing the large rRNA precursor synthesized by RNA polymerase I that encompasses sequences corresponding to mature 18S, 5.8S, and 25/28S rRNA. In humans, the identity of most enzymes responsible for individual processing steps, including endoribonucleases that cleave pre-rRNA at specific sites within regions flanking and separating mature rRNA, remains largely unknown. Here, we investigated the role of hUTP24 in rRNA maturation in human cells. hUTP24 is a human homolog of the Saccharomyces cerevisiae putative PIN domaincontaining endoribonuclease Utp24 (yUtp24), which was suggested to participate in the U3 snoRNA-dependent processing of yeast pre-rRNA at sites A 0 , A 1 , and A 2 . We demonstrate that hUTP24 interacts to some extent with proteins homologous to the components of the yeast small subunit (SSU) processome. Moreover, mutation in the putative catalytic site of hUTP24 results in slowed growth of cells and reduced metabolic activity. These effects are associated with a defect in biogenesis of the 40S ribosomal subunit, which results from decreased amounts of 18S rRNA as a consequence of inaccurate pre-rRNA processing at the 5 0 -end of the 18S rRNA segment (site A 1 ). Interestingly, and in contrast to yeast, site A 0 located upstream of A 1 is efficiently processed upon UTP24 dysfunction. Finally, hUTP24 inactivation leads to aberrant processing of 18S rRNA 2 nucleotides downstream of the normal A 1 cleavage site.

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Dxo1 is a new type of eukaryotic enzyme with both decapping and 5′-3′ exoribonuclease activity

Cited by 95 publications

References 43 publications

Multiple Nudix family proteins possess mRNA decapping activity

Multiple Nudix family proteins possess mRNA decapping activity

Healing for destruction: tRNA intron degradation in yeast is a two-step cytoplasmic process catalyzed by tRNA ligase Rlg1 and 5′-to-3′ exonuclease Xrn1

hUTP24 is essential for processing of the human rRNA precursor at site A₁, but not at site A₀

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Dxo1 is a new type of eukaryotic enzyme with both decapping and 5′-3′ exoribonuclease activity

Cited by 95 publications

References 43 publications

Multiple Nudix family proteins possess mRNA decapping activity

Multiple Nudix family proteins possess mRNA decapping activity

Healing for destruction: tRNA intron degradation in yeast is a two-step cytoplasmic process catalyzed by tRNA ligase Rlg1 and 5′-to-3′ exonuclease Xrn1

hUTP24 is essential for processing of the human rRNA precursor at site A1, but not at site A0

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hUTP24 is essential for processing of the human rRNA precursor at site A₁, but not at site A₀