Direct Interaction of the Spinal Muscular Atrophy Disease Protein SMN with the Small Nucleolar RNA-associated Protein Fibrillarin

Jones, Kevin W.; Gorzynski, Karen; Hales, Chadwick M.; Fischer, Utz; Badbanchi, Farah; Terns, Rebecca M.; Terns, Michael P.

doi:10.1074/jbc.m106161200

Cited by 151 publications

(143 citation statements)

References 69 publications

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“…SMN also binds directly to fibrillarin and GAR1, constituents of box C/D and box H/ACA small nucleolar RNPs (snoRNPs), respectively (Jones et al 2001;Pellizzoni et al 2001a). In vitro binding assays performed with full-length and truncated forms of the protein showed that SMN interacts directly with both fibrillarin and GAR1 and that the interactions are mediated by the RG-rich domains of fibrillarin and GAR1.…”

Section: A Role For the Smn Complex In The Biogenesis Of Other Rnpsmentioning

confidence: 99%

The SMN Complex: An Assembly Machine for RNPs

Battle¹,

Kasim²,

Yong³

et al. 2006

Cold Spring Harbor Symposia on Quantitative Biology

169

156

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Section: A Role For the Smn Complex In The Biogenesis Of Other Rnpsmentioning

confidence: 99%

The SMN Complex: An Assembly Machine for RNPs

Battle¹,

Kasim²,

Yong³

et al. 2006

Cold Spring Harbor Symposia on Quantitative Biology

169

156

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“…The N-terminal fragment of fibrillarin contains the glycine-and arginine-rich (GAR) domain (Fig. 4A) (25,26) responsible for interaction with other proteins such as spinal muscular atrophy disease protein (27). A deletion mutant, where the GAR domain was removed from GST-fibrillarin ( Fig.…”

Section: Orf3 Protein Does Not Localize To the Nucleolus In Fibrillarmentioning

confidence: 99%

Interaction of a plant virus-encoded protein with the major nucleolar protein fibrillarin is required for systemic virus infection

Kim¹,

MacFarlane²,

Калинина

et al. 2007

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

159

181

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The nucleolus and specific nucleolar proteins are involved in the life cycles of some plant and animal viruses, but the functions of these proteins and of nucleolar trafficking in virus infections are largely unknown. The ORF3 protein of the plant virus, groundnut rosette virus (an umbravirus), has been shown to cycle through the nucleus, passing through Cajal bodies to the nucleolus and then exiting back into the cytoplasm. This journey is absolutely required for the formation of viral ribonucleoprotein particles (RNPs) that, themselves, are essential for the spread of the virus to noninoculated leaves of the shoot tip. Here, we show that these processes rely on the interaction of the ORF3 protein with fibrillarin, a major nucleolar protein. Silencing of the fibrillarin gene prevents longdistance movement of groundnut rosette virus but does not affect viral replication or cell-to-cell movement. Repressing fibrillarin production also localizes the ORF3 protein to multiple Cajal bodylike aggregates that fail to fuse with the nucleolus. Umbraviral ORF3 protein and fibrillarin interact in vitro and, when mixed with umbravirus RNA, form an RNP complex. This complex has a filamentous structure with some regular helical features, resembling the RNP complex formed in vivo during umbravirus infection. The filaments formed in vitro are infectious when inoculated to plants, and their infectivity is resistant to RNase. These results demonstrate previously undescribed functions for fibrillarin as an essential component of translocatable viral RNPs and may have implications for other plant and animal viruses that interact with the nucleolus.Cajal bodies ͉ plant virus movement ͉ ribonucleoprotein particles T he nucleolus is a subnuclear domain and is the site of transcription and processing of rRNA and of ribosome biogenesis. In addition, the nucleolus also participates in other aspects of RNA metabolism and cell function (1, 2). The nucleolus is structurally and functionally associated with Cajal bodies (CBs), which are structures found in both animals and plants (3, 4). CBs contain different proteins including coilin, a protein essential for CB formation, and fibrillarin, a major nucleolar protein that is a core component of small nucleolar ribonucleoprotein particles (snoRNPs) and is required for rRNA processing (4-7). CBs are involved in the maturation of small nuclear RNPs (snRNPs) and snoRNPs, which traffic through CBs before accumulating in splicing speckles and the nucleolus, respectively (8, 9). Both the nucleolus and CBs have a role in RNA silencing in plants (10,11). Finally, a number of animal and plant viruses including the RNAcontaining tobacco etch virus and the DNA-containing tomato yellow leaf curl virus have a nucleolar phase in their life cycle (12, 13). Recently, we have shown that the ability of the umbravirus, groundnut rosette virus (GRV), to move long distances through the phloem, the specialized vascular system used by plants for the transport of assimilates and macromolecules, depends strictly on the...

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“…FIB co-localizes with the survival motor neuron (SMN) gene product in both nucleoli and Cajal bodies/gems of primary neurons (19,20). SMN is linked to one of the most common inheritable causes of childhood mortality, spinal muscular atrophy (19). In fact, a direct interaction between FIB and SMN has been demonstrated, although no functional basis for this interaction has been established, including any involvement of FIB in the pathogenesis of spinal muscular atrophy.…”

mentioning

confidence: 99%

“…The GAR domain is methylated at arginine residues, although the arginine methyltransferase responsible for in vivo methylation has not been identified (23,24). The GAR domain is responsible for the interaction of FIB with both SMN protein and the DEAD box RNA helicase p68 (19,21). A centrally located 90-residue sequence resembles an RNA-binding domain (RBD) present in various snRNPs.…”

mentioning

confidence: 99%

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Human Fibrillarin Forms a Sub-complex with Splicing Factor 2-associated p32, Protein Arginine Methyltransferases, and Tubulins α3 and β1 That Is Independent of Its Association with Preribosomal Ribonucleoprotein Complexes

Yanagida

Hayano

Yamauchi

et al. 2004

Journal of Biological Chemistry

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Fibrillarin (FIB, Nop1p in yeast) is an RNA methyltransferase found not only in the fibrillar region of the nucleolus but also in Cajal bodies. FIB is essential for efficient processing of preribosomal RNA during ribosome biogenesis, although its precise function in this process and its role in Cajal bodies remain uncertain. Here, we demonstrate that the human FIB N-terminal glycine-and arginine-rich domain (residues 1-77) and its spacer region 1 (78 -132) interact with splicing factor 2-associated p32 (SF2A-p32) and that the FIB methyltransferase-like domain (133-321) interacts with protein-arginine methyltransferase 5 (PRMT5, Janus kinase-binding protein 1). We also show that these proteins associate with several additional proteins, including PRMT1, tubulin ␣3, and tubulin ␤1 to form a sub-complex that is principally independent of the association of FIB with preribosomal ribonucleoprotein complexes that co-immunoprecipitate with the sub-complex in human cells expressing FLAG-tagged FIB. Based on the physical association of FIB with SF2A-p32 and PRMTs, as well as the other reported results, we propose that FIB may coordinate both RNA and protein methylation during the processes of ribosome biogenesis in the nucleolus and RNA editing such as small nuclear (nucleolar) ribonucleoprotein biogenesis in Cajal bodies.Fibrillarin (FIB) 1 is the most abundant protein in the fibrillar regions of the nucleolus where ribosomal RNA transcription and early preribosomal RNA (pre-rRNA) processing take place (1, 2). FIB is also found in Cajal bodies, subnuclear organelles that contain distinct components involved in RNA transcription and editing such as mRNA splicing and small nuclear (nucleolar) ribonucleoprotein (sn(o)RNP) biogenesis (3, 4). FIB is a component of a ribonucleoprotein (RNP) complex that contains U3, U8, and U13 small nucleolar RNAs that exhibit consensus sequence elements denoted box C (5Ј-UGAUGA-3Ј) and box D (5Ј-CUGA-3Ј) (5). The FIB RNP associates with Nop56p, Nop5p/58p, and a 15.5-kDa protein (a counterpart of yeast Snu13p) to form box C/D snoRNP complexes that function in site-specific 2Ј-O-methylation of pre-rRNA (6 -9). FIB is the methyltransferase that catalyzes this 2Ј-O-methylation (10).FIB, or Nop1p in the yeast Saccharomyces cerevisiae, is highly conserved in eukaryotes with respect to sequence, structure, and function (11-17). Deletion of the Nop1 gene in yeast results in inhibition of 2Ј-O-ribose methylation and pre-rRNA processing at sites A 0 to A 2 , indicating that Nop1p is directly involved in both pre-rRNA methylation and processing and ultimately in ribosome assembly (18). Although human FIB is the functional homolog of yeast Nop1p, it only partially complements a yeast nop1-defective mutant (15). Human FIB is a nucleolar autoantigen for the non-hereditary immune disease scleroderma (14). FIB co-localizes with the survival motor neuron (SMN) gene product in both nucleoli and Cajal bodies/gems of primary neurons (19,20). SMN is linked to one of the most common inheritable causes of childho...

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Direct Interaction of the Spinal Muscular Atrophy Disease Protein SMN with the Small Nucleolar RNA-associated Protein Fibrillarin

Cited by 151 publications

References 69 publications

The SMN Complex: An Assembly Machine for RNPs

The SMN Complex: An Assembly Machine for RNPs

Interaction of a plant virus-encoded protein with the major nucleolar protein fibrillarin is required for systemic virus infection

Human Fibrillarin Forms a Sub-complex with Splicing Factor 2-associated p32, Protein Arginine Methyltransferases, and Tubulins α3 and β1 That Is Independent of Its Association with Preribosomal Ribonucleoprotein Complexes

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