Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing

Ansel, K. Mark; Pastor, William A.; Rath, Nicola; Lapan, Ariya D.; Glasmacher, Elke; Wolf, Christine; Smith, Laura C.; Papadopoulou, Nikoletta; Lamperti, Edward D.; Tahiliani, Mamta; Ellwart, Joachim W.; Shi, Yujiang Geno; Kremmer, Elisabeth; Rao, Anjana; Heissmeyer, Vigo

doi:10.1038/nsmb.1417

Cited by 58 publications

(90 citation statements)

References 34 publications

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“…It is suggested that the peripheral area of mt-nucleoid may possess precursors of mitochondrial rRNA. In fact, 3Ј to 5Ј exonucleases including DEDDh superfamily protein are involved in the process of rRNA maturation, namely, RNA processing with 3Ј trimming in eukaryote nucleus (Ansel et al 2008, van Hoof et al 2000. It could be possible that Pmn34 is involved in such an rRNA maturation process.…”

Section: Resultsmentioning

confidence: 99%

New Protein Pmn34 with an Exonuclease Motif Localizes in the Mitochondrial Nucleoid Periphery of Physarum polycephalum

et al. 2009

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Summary Mitochondrial DNA (mtDNA) is highly organized into a compact structure, the mitochondrial nucleoid (mt-nucleoid). To facilitate our understanding of the regulation of mtDNA genetic activity within the mt-nucleoid structure, we have identified a novel mt-nucleoid protein Pmn34 (Physarum polycephalum mitochondrial nucleoid protein 34), having a molecular weight of 34 kDa, from pure mt-nucleoids isolated from the true slime mold, Physarum polycephalum. The Pmn34 protein is composed of 326 amino acids with mitochondrial transit peptides and its primary sequence contains a conserved 3Ј to 5Ј exonuclease motif of the "DEDD" superfamily. DNA mobility shift assays demonstrated that recombinant Pmn34 binds weakly to both mtDNA and lDNA with no apparent sequence specificity. Furthermore, immunoblotting and immunostaining analyses revealed that Pmn34 localizes specifically in the peripheral region of mt-nucleoids. These results indicate that Pmn34 functions in the peripheral region of mt-nucleoids, suggesting that the mt-nucleoid is compartmentalized into functional domains.

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Section: Resultsmentioning

confidence: 99%

New Protein Pmn34 with an Exonuclease Motif Localizes in the Mitochondrial Nucleoid Periphery of Physarum polycephalum

et al. 2009

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“…In addition to Las1L, Dom3Z, and Xrn2, our analysis of lowmolecular-weight RNAs (Fig. 10B) included targeting two conserved 3=-5= exoRNases, Eri1 and Isg20L2, with known or suspected functions in 5.8S rRNA 3=-end formation in mammals (1,9), the exosome subunit ExoSC10 (human Rrp6), and the ATPdependent 3=-5= RNA helicase Skiv2L2 (human Dob1/Mtr4). Skiv2L2 is a core exosome cofactor with known functions in 5.8S rRNA 3=-end formation in yeast and humans (10,39).…”

Section: Figmentioning

confidence: 99%

The Evolutionarily Conserved Protein LAS1 Is Required for Pre-rRNA Processing at Both Ends of ITS2

Schillewaert

Wacheul

Lhommé³

et al. 2012

Molecular and Cellular Biology

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Ribosome synthesis entails the formation of mature rRNAs from long precursor molecules, following a complex pre-rRNA processing pathway. Why the generation of mature rRNA ends is so complicated is unclear. Nor is it understood how pre-rRNA processing is coordinated at distant sites on pre-rRNA molecules. Here we characterized, in budding yeast and human cells, the evolutionarily conserved protein Las1. We found that, in both species, Las1 is required to process ITS2, which separates the 5.8S and 25S/28S rRNAs. In yeast, Las1 is required for pre-rRNA processing at both ends of ITS2. It is required for Rrp6-dependent formation of the 5.8S rRNA 3= end and for Rat1-dependent formation of the 25S rRNA 5= end. We further show that the Rat1-Rai1 5=-3= exoribonuclease (exoRNase) complex functionally connects processing at both ends of the 5.8S rRNA. We suggest that prerRNA processing is coordinated at both ends of 5.8S rRNA and both ends of ITS2, which are brought together by pre-rRNA folding, by an RNA processing complex. Consistently, we note the conspicuous presence of ϳ7-or 8-nucleotide extensions on both ends of 5.8S rRNA precursors and at the 5= end of pre-25S RNAs suggestive of a protected spacer fragment of similar length. Ribosomes are essential to all life forms. Ribogenesis is a major metabolic activity requiring the coordinated expression of the core RNA and protein components of the small and large subunits and also of a myriad of trans-acting protein and RNA factors, their maturation, packaging, and transport (reviewed in references 21, 29, and 42). Despite this great complexity, ribogenesis is an extremely robust process. Quality control and fail-safe mechanisms are available at all steps along the assembly pathway to ensure that a sufficient amount of functional ribosomes is provided at all times (reviewed in references 24 and 30).In eukaryotes, ribogenesis is initiated in the nucleolus. There, at the interface between the cortical side of fibrillar centers (FCs) and the surrounding dense fibrillar components (DFCs), RNA polymerase I is recruited and threaded along the ribosomal DNA (rDNA), producing pre-rRNA transcripts that extend into the DFC, where pre-rRNAs undergo cotranscriptional modification. In fast-growing budding yeast cells, up to 50 to 70% of pre-rRNA molecules are also subjected to cotranscriptional cleavage (3,23,28,36). Cotranscriptional cleavage occurs in internal transcribed spacer 1 (ITS1), separating the precursors destined to mature into the small and large ribosome subunit rRNAs, i.e., the 18S and 5.8S-25S rRNAs, respectively (28,36,47). This strategy, involving the cosynthesis of three of the four mature rRNAs from a single long transcript, contributes to coordinating the synthesis of the various components of the translational machinery. This strategy has been extensively conserved throughout evolution and predates the eukaryotes, since the Bacteria and Archaea also synthesize their rRNAs from polycistronic precursors (reviewed in reference 31).The synthesis of mature rRNAs relie...

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“…Recent work from Ramachandran and Chen (6) documented that an exoribonuclease encoded by small rna degrading nuclease (sdn) gene degrades mature miRNAs in Arabidopsis. Although in human cells the posttranscriptional control of miRNA is poorly defined, it can be hypothesized that enzymes involved in miRNA metabolism evolved from enzymes that process structural and/or catalytic RNAs, a view supported by the fact that a number of known molecules involved in small RNA metabolism also function in the processing of rRNAs (7,8).Exosome, a multiprotein complex of exonucleases, is an important component of the RNA processing machinery in eukaryotes and is essential for the processing of noncoding small RNAs (9-11). Human polynucleotide phosphorylase (hPNPase old-35 ), a highly evolutionarily conserved gene that catalyzes 3′-to-5′ phosphorolysis as well as 5′-to-3′ polymerization of RNA , acts as a trimer.…”

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confidence: 99%

Human polynucleotide phosphorylase selectively and preferentially degrades microRNA-221 in human melanoma cells

Das

Sokhi

Bhutia

et al. 2010

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

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MicroRNAs (miRNA), small noncoding RNAs, affect a broad range of biological processes, including tumorigenesis, by targeting gene products that directly regulate cell growth. Human polynucleotide phosphorylase (hPNPase old-35 ), a type I IFN-inducible 3′-5′ exoribonuclease, degrades specific mRNAs and small noncoding RNAs. The present study examined the effect of this enzyme on miRNA expression in human melanoma cells. miRNA microarray analysis of human melanoma cells infected with empty adenovirus or with an adenovirus expressing hPNPase old-35 identified miRNAs differentially and specifically regulated by hPNPase old-35 . One of these, miR-221, a regulator of the cyclin-dependent kinase inhibitor p27 kip1 , displayed robust down-regulation with ensuing up-regulation of p27 kip1 by expression of hPNPase old-35 , which also occurred in multiple human melanoma cells upon IFN-β treatment. Using both in vivo immunoprecipitation followed by Northern blotting and RNA degradation assays, we confirm that mature miR-221 is the target of hPNPase old-35 . Inhibition of hPNPase old-35 by shRNA or stable overexpression of miR-221 protected melanoma cells from IFN-β-mediated growth inhibition, accentuating the importance of hPNPase old-35 induction and miR-221 down-regulation in mediating IFN-β action. Moreover, we now uncover a mechanism of miRNA regulation involving selective enzymatic degradation. Targeted overexpression of hPNPase old-35 might provide an effective therapeutic strategy for miR-221-overexpressing and IFN-resistant tumors, such as melanoma.M icroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs that regulate gene expression at the posttranscriptional level and play important roles in a multiplicity of biological functions, including cell differentiation, tumorigenesis, apoptosis, and metabolism (1). miRNA genes are initially transcribed principally by either RNA polymerase II or RNA polymerase III as long primary transcripts, which are further processed by the nuclear RNase Drosha and cytoplasmic RNase Dicer to produce precursor miRNAs and mature miRNAs, respectively (2). miRNAs recognize and bind to partially complementary sites in the 3′ UTRs of target mRNAs, resulting in either translational repression or target degradation (3). The steadystate levels of miRNAs, crucial for its profound impact on a wide array of biological processes (4, 5), are presumably determined by the opposing activities of miRNA biogenesis and degradation. Although the framework of miRNA biogenesis is established, factors involved in miRNA dysregulation remain unknown. Recent work from Ramachandran and Chen (6) documented that an exoribonuclease encoded by small rna degrading nuclease (sdn) gene degrades mature miRNAs in Arabidopsis. Although in human cells the posttranscriptional control of miRNA is poorly defined, it can be hypothesized that enzymes involved in miRNA metabolism evolved from enzymes that process structural and/or catalytic RNAs, a view supported by the fact that a number of known molecules involved...

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Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing

Cited by 58 publications

References 34 publications

New Protein Pmn34 with an Exonuclease Motif Localizes in the Mitochondrial Nucleoid Periphery of Physarum polycephalum

New Protein Pmn34 with an Exonuclease Motif Localizes in the Mitochondrial Nucleoid Periphery of Physarum polycephalum

The Evolutionarily Conserved Protein LAS1 Is Required for Pre-rRNA Processing at Both Ends of ITS2

Human polynucleotide phosphorylase selectively and preferentially degrades microRNA-221 in human melanoma cells

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