A Conserved WD40 Protein Binds the Cajal Body Localization Signal of scaRNP Particles

Tycowski, Kazimierz T.; Shu, Mei‐Di; Kukoyi, Abiodun; Steitz, Joan A.

doi:10.1016/j.molcel.2009.02.020

Cited by 186 publications

(247 citation statements)

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“…Furthermore, localization of human scaRNA ACA57 to the CB was recently shown to require binding of a conserved WD40 protein to the CAB box (Tycowski et al, 2009). These experiments raise the question whether the CAB box and the WD40 protein might also be required for the modification reactions themselves.…”

Section: The Cab Box Is Not Required For Modification Of An Snrnamentioning

confidence: 99%

Section: Molecular Biology Of the Cell 5256mentioning

confidence: 99%

“…Using a nucleotide database search similar to that described by Tycowski et al (2009), we independently identified a guide RNA for 2Ј-O-methylation of Drosophila U4 snRNA at position A65. A standard RACE-PCR strategy was used to determine the 5Ј and 3Ј ends of the RNA.…”

Section: Templates For In Vitro Transcriptionmentioning

confidence: 99%

“…Drosophila U85 scaRNA is concentrated in the CB of the fly (Jády and Kiss, 2001;Liu et al, 2006bLiu et al, , 2009), where it pre-sumably directs the corresponding modifications of Drosophila U5 snRNA at C46 and U47. Two box H/ACA and several box C/D RNAs have been described as putative guide RNAs for modification of Drosophila snRNAs (Yuan et al, 2003;Huang et al, 2005a,b;Tycowski et al, 2009; Table 1). Independently, we identified one of these Drosophila guide RNAs, mgU4-65.…”

Section: Known and Predicted Guide Rnas For Nucleotide Modifications mentioning

confidence: 99%

“…These contain a related but somewhat different CAB box, which was shown to bind a conserved WD40 protein. Furthermore the CB localization of human ACA57 scaRNA was found to depend on its association with the WD40 protein (human WDR79; Tycowski et al, 2009).The conventional view, therefore, is the following. U1, U2, U4, and U5 are transcribed in the nucleus and quickly exported to the cytoplasm, where they assemble into snRNP particles.…”

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Small Cajal Body–specific RNAs ofDrosophilaFunction in the Absence of Cajal Bodies

Deryusheva

Gall

2009

MBoC

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During their biogenesis small nuclear RNAs (snRNAs) undergo multiple covalent modifications that require guide RNAs to direct methylase and pseudouridylase enzymes to the appropriate nucleotides. Because of their localization in the nuclear Cajal body (CB), these guide RNAs are known as small CB-specific RNAs (scaRNAs). Using a fluorescent primer extension technique, we mapped the modified nucleotides in Drosophila U1, U2, U4, and U5 snRNAs. By fluorescent in situ hybridization (FISH) we showed that seven Drosophila scaRNAs are concentrated in easily detectable CBs. We used two assays based on Xenopus oocyte nuclei to demonstrate that three of these Drosophila scaRNAs do, in fact, function as guide RNAs. In flies null for the CB marker protein coilin, CBs are absent and there are no localized FISH signals for the scaRNAs. Nevertheless, biochemical experiments show that scaRNAs are present at normal levels and snRNAs are properly modified. Our experiments demonstrate that several scaRNAs are concentrated as expected in the CBs of wild-type Drosophila, but they function equally well in the nucleoplasm of mutant flies that lack CBs. We propose that the snRNA modification machinery is not limited to CBs, but is dispersed throughout the nucleoplasm of cells in general. INTRODUCTIONThe two major ribosomal RNAs (rRNAs) and the spliceosomal small nuclear RNAs (snRNAs) U1, U2, U4, U5, and U6 contain many posttranscriptionally modified nucleotides, which are crucial for RNA-RNA and RNA-protein interactions, as well as spliceosome function (Yu et al., 1998; Yu, 2004, 2007). The most abundant modifications in both rRNAs and snRNAs are 2Ј-O-methylation and pseudouridylation, which are directed by small box C/D and box H/ACA guide RNAs, respectively. Each guide RNA molecule is associated with a set of four core proteins: box C/D RNAs form RNP particles with fibrillarin (the methyltransferase), Nop56, Nop58, and a 15.5-kDa protein, whereas box H/ACA RNAs associate with NAP57/dyskerin (the pseudouridine synthase), GAR1, NHP2, and NOP10 proteins (reviewed in Yu et al., 2004;Matera et al., 2007). Most guide RNAs are concentrated in the nucleolus, where they are involved in posttranscriptional modifications of rRNA. Because of their localization, they are referred to as small nucleolar RNAs (snoRNAs). However, the guide RNAs that mediate modification of the snRNAs are preferentially found in another nuclear organelle, the Cajal body (CB). These guide RNAs are called small CB-specific RNAs (scaRNAs).The first scaRNA to be studied in detail was U85 scaRNA (Jády and Kiss, 2001;Darzacq et al., 2002). U85 is a remarkable double guide RNA that contains both box C/D and box H/ACA motifs. In a set of detailed experiments it was shown that human U85 scaRNA guides both 2Ј-O-methylation at C45 and pseudouridylation at U46 in U5 snRNA. Modification takes place in the nucleus after import of the U5 snRNA from the cytoplasm . CB localization of U85 scaRNA was originally demonstrated by fluorescent in situ hybridization (FISH) in mammalian and ...

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Section: The Cab Box Is Not Required For Modification Of An Snrnamentioning

confidence: 99%

Section: Molecular Biology Of the Cell 5256mentioning

confidence: 99%

Section: Templates For In Vitro Transcriptionmentioning

confidence: 99%

Section: Known and Predicted Guide Rnas For Nucleotide Modifications mentioning

confidence: 99%

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Small Cajal Body–specific RNAs ofDrosophilaFunction in the Absence of Cajal Bodies

Deryusheva

Gall

2009

MBoC

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Small Nuclear Ribonucleoproteins (sn RNP s)

Stone

Riley

2014

Encyclopedia of Life Sciences

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Small nuclear ribonucleoproteins (snRNPs) are protein– ribonucleic acid (RNA) complexes defined by a core noncoding RNA of approximately 100–600 nucleotides and tightly bound proteins that together accumulate in the nucleus. The snRNPs are best known for their role in RNA splicing complexes, including U1, U2, U4, U5 and U6 snRNPs found in the spliceosome. Additional snRNPs are functionally diverse, but in many cases the RNA component of snRNPs can base‐pair with a substrate for precise alignment and possible catalysis. The U7 snRNP directs 3′‐end mRNA formation for histone transcripts, and the 7SK snRNP regulates transcription. Two special groups of snRNPs, small nucleolar RNPs (snoRNPs) and small Cajal‐body RNPs (scaRNPs) , are restricted to their named subnuclear compartments in order to direct post‐transcriptional modification of ribosomal and splicing RNAs, respectively. Certain herpesviruses express high levels of novel snRNPs involved in the regulation of gene expression. Due to their important biological roles, there are many diseases associated with snRNPs. Key Concepts: The snRNPs are small nuclear ribonucleoprotein particles, a class of dynamic RNA–protein complexes that accumulate in the nucleus. Major and minor splicing snRNPs form super‐complexes (spliceosomes) that direct the precise splicing of messenger RNAs. In the special process of trans ‐splicing, splice leader (SL) snRNPs donate RNA to the ends of transcripts. The U7 snRNP coordinates 3′ end processing of metazoan histone messenger RNAs. The 7SK snRNP regulates transcription by selectively sequestering and rendering inactive the P‐TEFb protein, a key modulator of RNA polymerase II. Two groups of snRNPs are singled out for specific subnuclear localisation: small nucleolar and small Cajal‐body associated (sno/scaRNPs) direct methylation and pseudouridylation of splicing and ribosomal RNAs. Some mammalian herpesviruses express viral snRNPs, which have enigmatic and complex functions in gene regulation. Several diseases including lupus present autoantibody production of antibodies directed at snRNP‐affiliated proteins such as Sm, Lsm and La. Most snRNPs have been affiliated with diseases and are therefore promising biomarkers for diagnosis and prognosis.

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Genetics of Dyskeratosis Congenita

Mason

Reeves

Perdigones

2013

Encyclopedia of Life Sciences

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Dyskeratosis congenita (DC) is a rare, inherited, skin and bone marrow failure disease. It is a multisystem disorder which is heterogeneous at the genetic and clinical levels. Genetically, nine genes have so far been identified whose mutation causes DC, and inheritance of the disease can be X linked, autosomal dominant or recessive. Clinically, the disease can present in childhood as classical DC with a characteristic triad of nail dystrophy, leukoplakia and abnormal skin pigmentation along with progressive bone marrow failure. More severe forms presenting in infancy and milder forms in adults, as aplastic anaemia or pulmonary fibrosis, exist. All forms of the disease with known pathogenesis are due to failure of telomere maintenance, often leading to stem cell exhaustion. Recent progress in the identification of mutations in human syndromes has revealed that DC overlaps clinically and genetically with a number of other rare syndromes. Key Concepts: The major cause of death in DC is bone marrow failure. The most common form of DC is X linked. In the X‐linked form, females are not, or very mildly, affected, but they show extremely skewed X‐inactivation, with cells expressing the mutated gene being outgrown by cells expressing the wild type gene. Dyskeratosis congenita is a disease caused by defective telomere maintenance. Nine genes have been discovered to cause dyskeratosis congenita when mutated, and their products are involved in telomerase and its assembly or as part of the telomere. When the disease is caused by mutations in the core components of telomerase, TERT and TERC families show an increase in severity of the disease in later generations, a phenomenon known as genetic anticipation. Genetic anticipation is due to shortening of telomeres from one generation to the next. Some DC mutations are also known causes of pulmonary fibrosis, liver fibrosis and Coats retinopathy. Now that genes responsible for rare syndromes are being discovered, it is becoming evident that there is overlap between DC and several other rare syndromes that have been described.

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A Conserved WD40 Protein Binds the Cajal Body Localization Signal of scaRNP Particles

Cited by 186 publications

References 47 publications

Small Cajal Body–specific RNAs ofDrosophilaFunction in the Absence of Cajal Bodies

Small Cajal Body–specific RNAs ofDrosophilaFunction in the Absence of Cajal Bodies

Small Nuclear Ribonucleoproteins (sn RNP s)

Genetics of Dyskeratosis Congenita

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