Assembly of the Nuclear Transcription and Processing Machinery: Cajal Bodies (Coiled Bodies) and Transcriptosomes

Gall, Joseph G.; Bellini, Michel; Wu, Zheng’an; Murphy, Christine

doi:10.1091/mbc.10.12.4385

Cited by 267 publications

(266 citation statements)

References 107 publications

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“…This hypothesis is in agreement with earlier electron microscopic observations of active transcription units that suggest that newly synthesized rRNAs are associated with RNA-binding proteins cotranscriptionally (reviewed by Miller, 1981;Osheim and Beyer 1998). Furthermore, recent studies in the RNA Pol II transcription system show that transcription factors are associated premRNA processing factors and may be recruited to the sites of transcription in the same complex (Gall et al, 1999) and that premRNA processing takes place cotranscriptionally (recently reviewed by Bentley, 1999). We propose that a similar situation may also take place during Pol I transcription.…”

Section: Direct Recruitment Of Nucleolar Factors To Nors Is Independesupporting

confidence: 91%

Initiation of Nucleolar Assembly Is Independent of RNA Polymerase I Transcription

Dousset

Wang

Verheggen

et al. 2000

MBoC

125

122

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This report examines the distribution of an RNA polymerase I transcription factor (upstream binding factor; UBF), pre-rRNA processing factors (nucleolin and fibrillarin), and pre-rRNAs throughout mitosis and postmitotic nucleologenesis in HeLa cells. The results demonstrate that nucleolin, fibrillarin, and pre-rRNAs synthesized at G2/M phase of the previous cell cycle are directly recruited to UBF-associated nucleolar organizer regions (NORs) early in telophase before chromosome decondensation. Unlike the fusion of prenucleolar bodies to the nucleoli, this early recruitment of processing factors and pre-rRNAs is independent of RNA polymerase I transcription. In the absence of polymerase I transcription, the initial localization of nucleolin, fibrillarin, and pre-rRNAs to UBF-associated NORs generates segregated mininucleoli that are similar to the larger ones observed in interphase cells grown under the same conditions. Pre-rRNAs are juxtaposed to UBF-nucleolin-fibrillarin caps that may represent the segregated nucleoli observed by electron microscopy. These findings lead to a revised model of nucleologenesis. We propose that nucleolar formation at the end of mitosis results from direct recruitment of processing factors and pre-rRNAs to UBF-associated NORs before or at the onset of rDNA transcription. This is followed by fusion of prepackaged prenucleolar bodies into the nucleolus. Pre-ribosomal ribonucleoproteins synthesized in the previous cell cycle may contribute to postmitotic nucleologenesis. INTRODUCTIONThe nucleus is a complex structure within which various functions and components are spatially and temporally organized and interregulated (reviewed by Lamond and Earnshaw, 1998;Dreyfuss and Struhl, 1999). Nucleoli represent the most prominent example of this organization. The major function of the nucleolus is ribosome biogenesis (reviewed by Busch and Smetana, 1970). rRNAs are synthesized, processed, cleaved, and assembled with ribosomal proteins in the nucleolus before export to the cytoplasm. The nucleolus is composed of three structurally distinguishable constituents: fibrillar centers, dense fibrillar components, and granular components, as observed by electron microscopy (reviewed by Busch and Smetana, 1970;Hadjiolov, 1985). Although the spatial and temporal relationship between rRNA synthesis and the three structural constituents remains to be clarified, it is generally thought that transcription of rDNA takes place in a transient area between the fibrillar centers and the dense fibrillar components and that rRNA processing and preribosomal particle assembly progress from the dense fibrillar components to the surrounding granular components (reviewed by Spector et al., 1993;Shaw and Jordan, 1995;Scheer and Hock, 1999). More recent evidence (reviewed by Pederson, 1998;Garcia and Pillus, 1999) suggests that nucleoli have additional functions related to the cell cycle Visintin et al., 1999), cellular aging (Straight et al., 1999), signal recognition particle biosynthesis (Jacobson and Pederson, 1998),...

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Section: Direct Recruitment Of Nucleolar Factors To Nors Is Independesupporting

confidence: 91%

Initiation of Nucleolar Assembly Is Independent of RNA Polymerase I Transcription

Dousset

Wang

Verheggen

et al. 2000

MBoC

125

122

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“…Two of these proteins, EAF1 and EAF2 (7,8), have been shown to colocalize with ELL in the nucleus in a stippled pattern that resembles that of Cajal bodies, structures that are enriched in factors involved in transcription and mRNA processing (9). Interestingly, Cajal bodies are disrupted in cells carrying the MLL-ELL translocation (10).…”

mentioning

confidence: 99%

ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL

Kong

Banks

Shilatifard

et al. 2005

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

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In human cells, the ELL family of transcription factors includes at least three members, which are all capable of stimulating the overall rate of elongation by RNA polymerase II by suppressing transient pausing by the enzyme at many sites along DNA. In this report, we identify the ELL-associated factors (EAF)1 and EAF2 as strong positive regulators of ELL elongation activity. Our findings provide insights into the structure and function of ELL family transcription factors, and they bring to light direct roles for the EAF proteins in regulation of RNA polymerase II transcription.elongation ͉ mRNA synthesis ͉ transcription ͉ transcription factor T he gene encoding the RNA polymerase II (pol II) elongation factor eleven-nineteen lysine-rich in leukemia (ELL) was first characterized as a fusion partner of the mixed lineage leukemia (MLL) gene in the (11, 19)(q23;p13.1) translocation in acute myeloid leukemia (1). The ELL protein has been shown to be capable of interacting with pol II and increasing its rate of transcript elongation in vitro by suppressing transient pausing by the enzyme (2, 3). Consistent with a role for ELL in controlling transcript elongation in vivo, Drosophila ELL colocalizes with pol II at transcriptionally active sites on polytene chromosomes, and evidence suggests that mutations in the gene encoding Drosophila ELL may preferentially affect synthesis of long transcripts (4).In addition to ELL, human cells have two ELL paralogs, ELL2 and ELL3, which can also stimulate the rate of elongation by pol II in vitro (5, 6). ELL and ELL2 are expressed in a wide variety of tissues in humans. ELL3, on the other hand, appears to be expressed predominantly in the testis (5, 6).A variety of ELL-interacting proteins have been identified through two-hybrid screens and biochemical purifications. Two of these proteins, EAF1 and EAF2 (7,8), have been shown to colocalize with ELL in the nucleus in a stippled pattern that resembles that of Cajal bodies, structures that are enriched in factors involved in transcription and mRNA processing (9). Interestingly, Cajal bodies are disrupted in cells carrying the MLL-ELL translocation (10).Suggesting that interactions between ELL and EAF1 may contribute to the leukemic phenotype of cells expressing the MLL-ELL chimera, the C-terminal domains of EAF1 and EAF2 share similarity with AF4 and ENL, other MLL translocation partners (7,8). In addition, expression of artificial MLL-EAF1 and MLL-EAF2 chimeras can immortalize hematopoetic progenitor cells and induce the development of acute myeloid leukemia in mice (7,8). Finally, and consistent with the possibility that EAF1 and EAF2 could play a role in transcriptional regulation, their C-terminal regions function as transcriptional activation domains when fused to the GAL4 DNA binding domain (7,8).In this article, we identify the EAF1 and EAF2 proteins as positive regulators of ELL elongation activity. Our findings provide insights into the mechanism of action of ELL family transcription factors, and they bring to light direct ro...

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“…All three RNA polymerases can be detected in Xenopus CBs and these structures have been suggested to be the site where RNA polymerase transcription and processing complexes are assembled (5). RNA polymerase I has not been detected in the CBs of a variety of cell lines under normal growth conditions (19).…”

Section: Discussionmentioning

confidence: 99%

“…Later, the same structure was characterized by electron microscopy as a round threaded non-membranelimited structure measuring 0.2 to 1.0 µm in diameter and denominated coiled body (2)(3)(4). Today, the structure is called Cajal body in honor of Ramon y Cajal (5).…”

Section: Introductionmentioning

confidence: 99%

Colocalization of coilin and nucleolar proteins in Cajal body-like structures of micronucleated PtK2 cells

Silva

Christofolini

Mortara

et al. 2004

Braz J Med Biol Res

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Cajal bodies (CB) are ubiquitous nuclear structures involved in the biogenesis of small nuclear ribonucleoproteins and show narrow association with the nucleolus. To identify possible relationships between CB and the nucleolus, the localization of coilin, a marker of CB, and of a set of nucleolar proteins was investigated in cultured PtK 2 cells undergoing micronucleation. Nocodazol-induced micronucleated cells were examined by double indirect immunofluorescence with antibodies against coilin, fibrillarin, NOR-90/hUBF, RNA polymerase I, PM/Scl, and To/Th. Cells were imaged on a BioRad 1024-UV confocal system attached to a Zeiss Axiovert 100 microscope. Since PtK 2 cells possess only one nucleolus organizer region, micronucleated cells presented only one or two micronuclei containing nucleolus. By confocal microscopy we showed that in most micronuclei lacking a typical nucleolus a variable number of round structures were stained by antibodies against fibrillarin, NOR-90/hUBF protein, and coilin. These bodies were regarded as CB-like structures and were not stained by anti-PM/Scl and anti-To/Th antibodies. Anti-RNA polymerase I antibodies also reacted with CB-like structures in some micronuclei lacking nucleolus. The demonstration that a set of proteins involved in RNA/RNP biogenesis, namely coilin, fibrillarin, NOR-90/hUBF, and RNA polymerase I gather in CB-like structures present in nucleolidevoid micronuclei may contribute to shed some light into the understanding of CB function.

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Assembly of the Nuclear Transcription and Processing Machinery: Cajal Bodies (Coiled Bodies) and Transcriptosomes

Cited by 267 publications

References 107 publications

Initiation of Nucleolar Assembly Is Independent of RNA Polymerase I Transcription

Initiation of Nucleolar Assembly Is Independent of RNA Polymerase I Transcription

ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL

Colocalization of coilin and nucleolar proteins in Cajal body-like structures of micronucleated PtK2 cells

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