The NYN Domains: Novel Predicted RNAses with a PIN Domain-Like Fold

Anantharaman, Vivek; Aravind, L.

doi:10.4161/rna.3.1.2548

Cited by 124 publications

(159 citation statements)

References 67 publications

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“…The structure of the metallonuclease domain of PRORP1 is a unique high-resolution structure of a Nedd4-BP1, YacP nuclease (NYN) domain, a distinct ribonuclease family member of the PilT N-terminal (PIN) domain-like fold superfamily (18). This structure resembles the nuclease domains of DNA polymerase I and FLAP nucleases; the closest metallonuclease domain structural homologs include Taq polymerase (19) and human exonuclease 1 (20) (hExo1; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The metallonuclease domain of PRORP1 provides insight into the active-site architecture, metal dependence, and potential functional roles of active-site side chains in the broad family of NYN domain-containing proteins. The prototypical NYN domain is found across all kingdoms of life, often fused to RNA-binding motifs (18). These domains have evolved to play important roles in RNA processing and they are overrepresented in eukaryotic The anomalous difference 2Fo-Fc electron density map, contoured at 3σ, is shown in yellow and is superimposed on the PRORP1 structure.…”

Section: Discussionmentioning

confidence: 99%

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Mitochondrial ribonuclease P structure provides insight into the evolution of catalytic strategies for precursor-tRNA 5′ processing

Howard¹,

Lim²,

Fierke

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

110

235

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Ribonuclease P (RNase P) catalyzes the maturation of the 5′ end of tRNA precursors. Typically these enzymes are ribonucleoproteins with a conserved RNA component responsible for catalysis. However, protein-only RNase P (PRORP) enzymes process precursor tRNAs in human mitochondria and in all tRNA-using compartments of Arabidopsis thaliana. PRORP enzymes are nuclear encoded and conserved among many eukaryotes, having evolved recently as yeast mitochondrial genomes encode an RNase P RNA. Here we report the crystal structure of PRORP1 from A. thaliana at 1.75 Å resolution, revealing a prototypical metallonuclease domain tethered to a pentatricopeptide repeat (PPR) domain by a structural zinc-binding domain. The metallonuclease domain is a unique high-resolution structure of a Nedd4-BP1, YacP Nucleases (NYN) domain that is a member of the PIN domain-like fold superfamily, including the FLAP nuclease family. The structural similarity between PRORP1 and the FLAP nuclease family suggests that they evolved from a common ancestor. Biochemical data reveal that conserved aspartate residues in PRORP1 are important for catalytic activity and metal binding and that the PPR domain also enhances activity, likely through an interaction with pre-tRNA. These results provide a foundation for understanding tRNA maturation in organelles. Furthermore, these studies allow for a molecular-level comparison of the catalytic strategies used by the only known naturally evolved protein and RNA-based catalysts that perform the same biological function, pre-tRNA maturation, thereby providing insight into the differences between the prebiotic RNA world and the present protein-dominated world.catalytic mechanism | magnesium | molecular recognition A ccording to the RNA world hypothesis, RNA played dual roles as carrier of genetic information and catalyst in a prebiotic world. However, over eons of evolution, proteins with their expanded 20-aa alphabet and greater structural and functional complexity took over many RNA-based functions. Structural insights into this evolutionary transition are limited because of the lack of examples of RNA and protein macromolecules that perform the same biological function in nature. One notable exception is ribonuclease P (RNase P) that catalyzes maturation of the 5′ end of tRNA across all domains of life. Until recently, all known RNase P enzymes included a catalytic RNA component. The discovery of a protein-only RNase P [proteinacous RNase P (PRORP)] from human mitochondria and Arabidopsis thaliana has dramatically shifted this paradigm (1-3). These enzymes represent a unique class of metallonucleases and are conserved among many eukaroytes (1, 2). A. thaliana encodes three PRORP enzymes (PRORP1, -2, and -3) that catalyze pretRNA processing (2). PRORP1 localizes to the mitochondria and chloroplast whereas PRORP2 and PRORP3 localize to the nucleus (2), suggesting that protein-based enzymes catalyze pretRNA maturation in these cellular locations (2, 3). To gain mechanistic and evolutionary insights into the PRORP...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mitochondrial ribonuclease P structure provides insight into the evolution of catalytic strategies for precursor-tRNA 5′ processing

Howard¹,

Lim²,

Fierke

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

110

235

View full text Add to dashboard Cite

show abstract

“…The putative PRORP RNase P enzymes are characterized by the occurrence of a conserved ''NYN'' metallonuclease domain (Anantharaman and Aravind 2006). PRORP proteins also belong to the huge pentatricopeptide repeat (PPR) protein family.…”

mentioning

confidence: 99%

PRORP proteins support RNase P activity in both organelles and the nucleus in Arabidopsis

Gutmann¹,

Gobert²,

Giegé³

2012

Genes Dev.

120

167

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RNase P is an essential enzyme that cleaves the 59 leader sequence of tRNA precursors. RNase Ps were believed until now to occur universally as ribonucleoproteins in organisms performing RNase P activity. Here we find that protein-only RNase P enzymes called PRORP (for proteinaceous RNase P) support RNase P activity in vivo in both organelles and the nucleus in Arabidopsis. Beyond tRNA, PRORP proteins are involved in the maturation of small nucleolar RNA (snoRNA) and mRNA. Finally, ribonucleoprotein RNase MRP is not involved in tRNA maturation in plants. Altogether, our results indicate that ribonucleoprotein enzymes have been entirely replaced by proteins for RNase P activity in plants.Supplemental material is available for this article.Received February 10, 2012; revised version accepted April 5, 2012.RNase P is a virtually universal enzyme involved in the maturation of tRNAs, as it cleaves the 59 leader sequence of tRNA precursors. It is thus essential to obtain functional tRNAs and is therefore pivotal for translation (Lai et al. 2010;Reiter et al. 2010). RNase P activities from all phyla of life were assumed to be universally performed by ribonucleoprotein enzymes whose catalytic activities are held by ribozymes (Altman 2007). This concept was first challenged with the proposition that spinach chloroplast and human mitochondria RNase Ps would not contain any RNA moiety (Wang et al. 1988;Rossmanith and Karwan 1998). More recently, protein-only RNase P enzymes called PRORP (for proteinaceous RNase P) have been characterized at the molecular level in endosymbiotic organelles in both humans and Arabidopsis (Holzmann et al. 2008;Gobert et al. 2010). Still, the dogma remained that RNase P enzymes would nonetheless universally occur as ribonucleoproteins in living organisms performing RNase P activity, with protein-only RNase Ps being marginal exceptions restricted to only some organelles (e.g., Esakova and Krasilnikov 2010).The putative PRORP RNase P enzymes are characterized by the occurrence of a conserved ''NYN'' metallonuclease domain (Anantharaman and Aravind 2006). PRORP proteins also belong to the huge pentatricopeptide repeat (PPR) protein family. These proteins, typically from eukaryotes, are involved in a wide variety of posttranscriptional mechanisms (Schmitz-Linneweber and Small 2008). However, no functional information was available for PRORP proteins. We previously established that Arabidopsis PRORP1, a protein localized in organelles, can act in vitro as an RNase P enzyme that is a single protein (Gobert et al. 2010), although its function remained elusive in planta. We also used localization experiments (YFP fusions and immunodetections) to determine that PRORP2 and PRORP3, two paralogs of PRORP1, were present in Arabidopsis nuclei (Gobert et al. 2010). In addition, the fast-growing amount of genomic data has revealed that some important groups of eukaryotes, such as land plants and kinetoplastids, do not encode any recognizable genes for RNase P RNA or for proteins specific for ribonucleoprotein...

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“…1A) (7). The NYN domain is a novel metallonuclease domain sharing structural homology to the PIN (PilT N terminus) and flap nuclease families (8). NYN domains have a relatively exposed active site and contain four conserved aspartates as compared with the flap nuclease family that has six conserved aspartates (7,8).…”

mentioning

confidence: 99%

Mechanistic Studies Reveal Similar Catalytic Strategies for Phosphodiester Bond Hydrolysis by Protein-only and RNA-dependent Ribonuclease P

Howard¹,

Klemm²,

Fierke

2015

Journal of Biological Chemistry

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The NYN Domains: Novel Predicted RNAses with a PIN Domain-Like Fold

Cited by 124 publications

References 67 publications

Mitochondrial ribonuclease P structure provides insight into the evolution of catalytic strategies for precursor-tRNA 5′ processing

Mitochondrial ribonuclease P structure provides insight into the evolution of catalytic strategies for precursor-tRNA 5′ processing

PRORP proteins support RNase P activity in both organelles and the nucleus in Arabidopsis

Mechanistic Studies Reveal Similar Catalytic Strategies for Phosphodiester Bond Hydrolysis by Protein-only and RNA-dependent Ribonuclease P

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