hNaf1 is required for accumulation of human box H/ACA snoRNPs, scaRNPs, and telomerase

Hoareau-Aveilla, Coralie; Bonoli, Matteo; Caizergues‐Ferrer, Michèle; Henry, Y.

doi:10.1261/rna.2344106

Cited by 52 publications

(52 citation statements)

References 44 publications

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“…Human NAF1 is concentrated in the nucleus but excluded from sites of mature H/ACA RNPs, the nucleoli and Cajal bodies (Darzacq et al 2006;Hoareau-Aveilla et al 2006). Surprisingly, when NAF1 was fused to the green fluorescent protein (GFP) and transiently expressed, it accumulated mostly in the cytoplasm (Fig.…”

Section: Differential Localization and Abundance Of Endogenous And Exmentioning

confidence: 99%

“…This lack of cellular association of NAF1 with mature H/ACA RNPs is further supported by the failure of NAF1 to concentrate in nucleoli and Cajal bodies, the sites of mature H/ACA RNPs (Darzacq et al 2006;Hoareau-Aveilla et al 2006). To test if overexpression of NAF1 in the nucleus could overcome this lack of association, GFP-NAF1 was transiently expressed in COS cells and concentrated in the nuclei by addition of LMB to prevent its export.…”

Section: Exchange Of H/aca Rnp Proteins In Cell Lysatesmentioning

confidence: 99%

“…They all consist of one of the z200 different H/ACA RNAs and the same four evolutionary conserved core proteins, NAP57 (dyskerin or Cbf5p in yeast), NOP10, NHP2 (forming a core trimer), and GAR1 (Smith and Steitz 1997;Kiss 2001;Filipowicz and Pogacic 2002;Decatur and Fournier 2003;Meier 2005). In human cells, formation of these particles and consequent stabilization of the H/ACA RNA depends on at least one nuclear assembly factor, NAF1 (Darzacq et al 2006;Hoareau-Aveilla et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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Dynamic association and localization of human H/ACA RNP proteins

Kittur¹,

Darzacq²,

Roy³

et al. 2006

RNA

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Mammalian H/ACA RNPs are essential for ribosome biogenesis, pre-mRNA splicing, and telomere maintenance. To form mature RNA-protein complexes, one H/ACA RNA associates with four core proteins. In the cell, this process is assisted by at least one nuclear assembly factor, NAF1. Here we report several unanticipated dynamic aspects of H/ACA RNP proteins. First, when overexpressed, NAF1 delocalizes to the cytoplasm. However, its nucleocytoplasmic shuttling properties remain unaffected. These observations demonstrate a subtle equilibrium between NAF1 expression levels and the availability of NAF1 nuclear binding sites. Second, although NAF1 is excluded from mature RNPs in nucleoli and Cajal bodies, NAF1 associates with mature H/ACA RNA in cell lysates. This association occurs post-lysis because it is observed even when NAF1 and the H/ACA RNA are expressed in separate cells. This documents a protein-RNP association in cell lysates that is absent from intact cells. Third, in similar experiments, all H/ACA core proteins, except NAP57, exchange with their exogenous counterparts, portraying an unexpected dynamic picture of H/ACA RNPs. Finally, the irreversible association of only NAP57 with H/ACA RNA and the conundrum that only NAP57 is mutated in X-linked dyskeratosis congenita (even though most core proteins are required for maintaining H/ACA RNAs) may be more than a coincidence.

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Section: Differential Localization and Abundance Of Endogenous And Exmentioning

confidence: 99%

Section: Exchange Of H/aca Rnp Proteins In Cell Lysatesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamic association and localization of human H/ACA RNP proteins

Kittur¹,

Darzacq²,

Roy³

et al. 2006

RNA

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“…Dyskerin, NHP2 and NOP10 are deposited cotranscriptionally with the help of the H/ACA RNP assembly chaperone NAF1, which is subsequently exchanged for GAR1 (Darzacq et al, 2006). Dyskerin, NHP2 and NOP10 have been identified by mass spectrometry in affinity purified human telomerase (Fu and Collins, 2007;Cohen et al, 2007) and are all essential for the stability of hTR and the other human H/ ACA-motif snoRNAs in vivo (Hoareau-Aveilla et al, 2006;Fu and Collins, 2007;Walne et al, 2007). GAR1 is important for localization of H/ACA-motif snoRNAs to the nucleolus in yeast, and it is important for the dyskerin-mediated catalysis of pseudouridine formation within a H/ACA-motif snoRNP (Ye, 2007).…”

Section: Biogenesis Of Mature Telomerase Rna and Telomerase Rnpmentioning

confidence: 99%

Physiological assembly and activity of human telomerase complexes

Collins

2008

Mechanisms of Ageing and Development

104

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Telomerase is a specialized reverse transcriptase conserved throughout almost all eukaryotic life. It plays a fundamental role in genome maintenance, adding back the telomeric DNA repeats lost from chromosome ends due to incomplete replication or damage. The protein and RNA subunits of telomerase fold and function in a co-dependent manner to establish a high fidelity of telomeric repeat synthesis. Over the past two decades, studies of telomerase have uncovered previously unanticipated levels of complexity in its assembly, activity and regulation. This review describes the current understanding of telomerase in humans, with particular focus on telomerase biogenesis and regulation in its cellular context.

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“…Many of these, such as NAF1, pontin and reptin, aid in RNP assembly but do not remain associated with the mature telomerase enzyme. 17,18 A few, however, including NOP10, NHP2 and GAR1, remain stably associated with the mature RNP and are presumed to play additional roles in stability, regulation or trafficking. 19,20 To identify new proteins that interact with dyskerin that may be important for telomerase function, we purified dyskerin complexes from human cancer cells and identified co-purifying proteins by mass spectrometry.…”

mentioning

confidence: 99%