Nucleolar localization signals of Box H/ACA small nucleolar RNAs

Narayanan, Aarthi; Lukowiak, Andrew A.; Jády, Beáta E.; Dragon, François; Kiss, Tamás; Terns, Rebecca M.; Terns, Michael P.

doi:10.1093/emboj/18.18.5120

Cited by 119 publications

(94 citation statements)

References 53 publications

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“…Conversely, although deletion of the H-box leads to a decrease in vTR accumulation in total extract, most of the RNA detected is found in the nucleus. Thus, the H-box of vTR seems more likely to be involved in nucleolar targeting as previously shown for hTR (20,21).…”

Section: Discussionsupporting

confidence: 69%

“…The third domain, the H/ACA CR7 domain, is dispensable for in vitro telomerase activity but essential for TR activity in vivo. Indeed, this domain is involved in the nuclear and nucleolar targeting of TR, resulting in 3Ј-end processing and their intracellular stability (20,21). The relevance of this domain was illustrated by studies on the dyskeratosis congenital disorder affecting especially the bone marrow and skin.…”

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confidence: 99%

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Comparative Functional Study of the Viral Telomerase RNA Based on Natural Mutations

Fragnet¹,

Kut²,

Rasschaert³

2005

Journal of Biological Chemistry

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Telomerase activity is present in most malignant tumors and provides a mechanism for the unlimited potential for division of neoplastic cells. We previously characterized the first identified viral telomerase RNA (vTR) encoded by the Marek's disease virus (MDV) (Fragnet, L., Blasco, M. A., Klapper, W., and Rasschaert, D. (2003) J. Virol. 77, 5985-5996). This avian herpesvirus induces T-lymphomas. We demonstrated that the vTR subunit of the oncogenic MDV-RB1B strain is functional and would be more efficient than its chicken counterpart, cTR, which is 88% homologous. We take advantage of the functionality of those natural mutant TRs to investigate the involvement of the mutations of vTR on its efficiency in a heterologous murine cell system and in a homologous in vitro system using the recombinant chicken telomerase reverse transcriptase. The P2 helix of the pseudoknot seems to be more stable in vTR than in cTR, and this may account for the higher activity of vTR than cTR. Moreover, the five adenines just upstream from the P3 helix of vTR may also play an important role in its efficiency. We also established that the substitution of a single nucleotide at the 3-extremity of the H-box of the vaccine MDV-Rispens strain vTR resulted in a lack of its accumulation within the cell, especially in the nucleus, correlated with a decrease in telomerase activity.Telomeres are nucleoprotein structures found at the extremities of eukaryotic linear chromosomes (1). They are essential for chromosome stability, and thus, genome rearrangements, the cell cycle, and carcinogenesis depend directly on the integrity of these structures (2). Telomeres are composed of tandemly repeated DNA sequences, which consist of 5Ј-GGT-TAG-3Ј hexamers in vertebrates. Telomeres replicate by a specific mechanism involving telomerase, a ribonucleoprotein complex that serves as the preferential system for compensating the erosion of telomeres at each round of DNA replication (3). The minimal telomerase complex sufficient for in vitro activity comprises two major components: 1) a protein subunit (TERT) 1 with reverse transcriptase activity associated with 2)an RNA subunit (TR) containing a short template sequence specific for telomere repeats (4). Telomerase activity is tightly regulated in cells. According to the constitution of the minimal telomerase complex, the regulation of the telomerase activity would rest on either the expression of the TERT or the TR subunits, as described in human or mouse, respectively. In addition, telomerase is not detectable in normal somatic cells but is strongly expressed during fetal development and constitutively expressed in highly proliferative postnatal cells such as germ line cells, stem cells, and lymphocytes (5, 6). Furthermore, high levels of telomerase activity are also detected in a large range of cancers (at least 85%) and are closely associated with immortalization processes (7, 8).In the last three years, a correlation has been established between telomerase activity and viral infections with the oncogenic p...

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Section: Discussionsupporting

confidence: 69%

mentioning

confidence: 99%

Comparative Functional Study of the Viral Telomerase RNA Based on Natural Mutations

Fragnet¹,

Kut²,

Rasschaert³

2005

Journal of Biological Chemistry

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“…Both types of snoRNAs are targeted to nucleoli Narayanan et al 1999), where they modify rRNAs. Likewise, scaRNAs are targeted to Cajal bodies for snRNA modification (Richard et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Maturation of mammalian H/ACA box snoRNAs: PAPD5-dependent adenylation and PARN-dependent trimming

Berndt¹,

Harnisch²,

Rammelt³

et al. 2012

RNA

137

171

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Small nucleolar and small Cajal body RNAs (snoRNAs and scaRNAs) of the H/ACA box and C/D box type are generated by exonucleolytic shortening of longer precursors. Removal of the last few nucleotides at the 39 end is known to be a distinct step. We report that, in human cells, knock-down of the poly(A) specific ribonuclease (PARN), previously implicated only in mRNA metabolism, causes the accumulation of oligoadenylated processing intermediates of H/ACA box but not C/D box RNAs. In agreement with a role of PARN in snoRNA and scaRNA processing, the enzyme is concentrated in nucleoli and Cajal bodies. Oligo(A) tails are attached to a short stub of intron sequence remaining beyond the mature 39 end of the snoRNAs. The noncanonical poly(A) polymerase PAPD5 is responsible for addition of the oligo(A) tails. We suggest that deadenylation is coupled to clean 39 end trimming, which might serve to enhance snoRNA stability.

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“…In contrast to splicing snRNPs, their biogenesis is thought to occur exclusively within the nucleus with no cytoplasmic stage (Terns and Dahlberg, 1994). Like splicing snRNPs, the box C/D snoRNPs localize transiently to CBs before reaching their steady-state localization in nucleoli (Narayanan et al, 1999). Hypermethylation of the 5Ј cap of the snoRNA, analogous to one of the cytoplasmic events in snRNP maturation, occurs in the CB Verheggen et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

A regulatory role for CRM1 in the multi-directional trafficking of splicing snRNPs in the mammalian nucleus

Sleeman

2007

Journal of Cell Science

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Distinct pathways of ribonucleoprotein transport exist within the nucleus, connected to their biogenesis and maturation. These occur despite evidence that the major mechanism for their movement within the nucleus is passive diffusion. Using fusions of Sm proteins to YFP, CFP and photoactivatable GFP, I have demonstrated that pathways with uni-directional bulk flow of complexes can be maintained within the nucleus despite multi-directional exchange of individual complexes. Newly imported splicing small nuclear ribonucleoproteins (snRNPs) exchange between Cajal bodies (CBs) within a nucleus and access the cytoplasm, but are unable to accumulate in speckles. By contrast, snRNPs at steady-state exchange freely in any direction between CBs and speckles, but cannot leave the nucleus. In addition to these surprising qualitative observations in the behaviour of nuclear complexes, sensitive live-cell microscopy techniques can detect subtle quantitative disturbances in nuclear dynamics before they have had an effect on overall nuclear organization. Inhibition of the nuclear export factor, CRM1, using leptomycin B results in a change in the dynamics of interaction of newly imported snRNPs with CBs. Together with the detection of interactions of CRM1 with Sm proteins and the survival of motor neurons (SMN) protein, these studies suggest that the export receptor CRM1 is a key player in the molecular mechanism for maintaining these pathways. Its role in snRNP trafficking, however, appears to be distinct from its previously identified role in small nucleolar RNP (snoRNP) maturation.

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Nucleolar localization signals of Box H/ACA small nucleolar RNAs

Cited by 119 publications

References 53 publications

Comparative Functional Study of the Viral Telomerase RNA Based on Natural Mutations

Comparative Functional Study of the Viral Telomerase RNA Based on Natural Mutations

Maturation of mammalian H/ACA box snoRNAs: PAPD5-dependent adenylation and PARN-dependent trimming

A regulatory role for CRM1 in the multi-directional trafficking of splicing snRNPs in the mammalian nucleus

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