Ribosome Biogenesis: From Structure to Dynamics

doi:10.1016/S1937-6448(10)84002-X

International Review of Cell and Molecular Biology

Volume 284, 2010, Pages 67-111

https://doi.org/10.1016/S1937-6448(10)84002-X Get rights and content

Abstract

In this chapter we describe the status of the research concerning the nucleolus, the major nuclear body. The nucleolus has been recognized as a dynamic organelle with many more functions than one could imagine. In fact, in addition to its fundamental role in the biogenesis of preribosomes, the nucleolus takes part in many other cellular processes and functions, such as the cell-cycle control and the p53 pathway: the direct or indirect involvement of the nucleolus in these various processes makes it sensitive to their alteration. Moreover, it is worth noting that the different nucleolar factors participating to independent mechanisms show different dynamics of association/disassociation with the nucleolar body.

Introduction

The nucleolus is the most prominent feature of the cell nucleus. When Fontana (1781) noticed it first, he described a specific spot inside the nucleus; however, he ignored that he was observing the only point where one can exactly localize the presence of specific genes without any special techniques.

Ribosomal genes are present in many repeats which are differently amplified in different species (Cmarko et al., 2008) up to a point where it has become generally accepted to assert that two genomes existed, the nuclear genome and the nucleolar one. These two genomes work together and mutually influence each other; as it has become more and more clear in these last years, some nucleolar functions are strictly related to nuclear functions (Martin et al., 2009, Pederson & Tsai, 2009).

Many reviews have been devoted to the nucleolus, both in animal and in plant cells, and this organelle has been studied and observed under many different aspects. In this chapter, we will mainly consider the nucleolus and its activity in view of the dynamics connected to ribosome biogenesis, integrating new concepts into an old story.

Section snippets

Morphology and cytochemistry

Structure and function are, as usual, strictly related and the nucleolus is no exception.

At light microscopy, it has long been studied and some of its inner structures described; some were more or less corresponding to reality, such as the “nucleolini” described as prominent inside nucleoli and later recognized to be fibrillar centers (FCs; Love and Wildy, 1963). The nucleolar body is clearly identified in the nucleus when stained by a vital fluorescent probe such as SYTO RNASelect (S32703,

Extra situm

Nucleolar transcription has been studied extra situm since 1969 when Miller and coworkers devised a technique for spreading nucleoli. The surprising result was the presence of the transcription units in the form of Christmas trees. It was soon realized that along the DNA axis each RNA branch developed from a small knob, which was recognized to be the RNA polymerase I, while at the distal terminus of the branch, a terminal knob is present. This knob has been shown to be constituted by U3 snRNPs

Ribosome Dynamics

The proof of the nucleolar dynamism is represented by the continuous exchange of molecules between the organelle and the nucleoplasm in response to specific cellular needs. In this transfer of proteins, obviously leading to a temporary specific distribution of a factor, distinct signals or pathways should exist to determine the retention or the release of a factor from the nucleolus.

Emmott and Hiscox (2009) propose the idea that the nucleolus is assembled on the basis of a core of nucleolar

Concluding Remarks

The nucleolus is a fascinating structure, and after more than 200 years since its discovery still retains many secrets. Perhaps the most intriguing characteristics are its plasticity, and the dynamics behind. These features not only involve the spatial organization of the nucleolus but also its functions. Besides being the ribosomal factory of the cell, the nucleolus has probably several other functions and involvements, and researchers have just begun to unveil some of these roles. The next

Acknowledgments

This work was supported by the Fondo di Ateneo per la Ricerca (FAR 2009). The authors would like to thank all the people who supported them during this endless task.

This chapter is dedicated to the memory of Prof. Maria Gabriella Manfredi Romanini, who now knows all the answers.

References (270)

V.G. Allfrey
Nuclear ribosomes, messenger-RNA and protein synthesis
Exp. Cell Res.
(1963)
J.S. Andersen et al.
Directed proteomic analysis of the human nucleolus
Curr. Biol.
(2002)
J. Bassler et al.
The NUG1 GTPase reveals and N-terminal RNA-binding domain that is essential for association with 60 S pre-ribosomal particles
J. Biol. Chem.
(2006)
W. Bernhard
A new staining procedure for electron microscopical cytology
J. Ultrastruct. Res.
(1969)
M. Biggiogera et al.
Physiologically inactive nucleoli contain nucleoplasmic ribonucleoproteins: immunoelectron microscopy of mouse spermatids and early embryos
Exp. Cell Res.
(1994)
M. Biggiogera et al.
Still immunodetectable nuclear RNPs are extruded from the cytoplasm of spontaneously apoptotic thymocytes
Exp. Cell Res.
(1997)
M. Biggiogera et al.
Rearrangement of nuclear ribonucleoprotein (RNP)-containing structures during apoptosis and transcriptional arrest
Biol. Cell
(2004)
P.B. Billings et al.
Proteins of nuclear ribonucleoprotein subcomplexes
Methods Cell Biol.
(1978)
S. Boulon et al.
PHAX and CRM1 are required sequentially to transport U3 snoRNA to nucleoli
Mol. Cell
(2004)
B. Bradatsch et al.
Arx1 functions as an unorthodox nuclear export receptor for the 60S preribosomal subunit
Mol. Cell
(2007)

D.E. Brodersen et al.

Crystal structure of the 30 S ribosomal subunit from Thermus thermophilus: structure of the proteins and their interactions with 16 S RNA

J. Mol. Biol.

(2002)

I. Casafont et al.

The giant fibrillar center: a nucleolar structure enriched in upstream binding factor (UBF) that appears in transcriptionally more active sensory ganglia neurons

J. Struct. Biol.

(2007)

C.H. Chuang et al.

Long-range directional movement of an interphase chromosome site

Curr. Biol.

(2006)

C. Clevenger et al.

Identification of a nuclear protein component of interchromatin granules using a monoclonal antibody and immunogold electron microscopy

Exp. Cell Res.

(1984)

T. David-Pfeuty

The flexible evolutionary anchorage-dependent Pardee's restriction point of mammalian cells: how its deregulation may lead to cancer

Biochim. Biophys. Acta

(2006)

M. Derenzini et al.

Interphase nucleolar organizer regions in cancer cells

Int. Rev. Exp. Pathol.

(1991)

M. Derenzini et al.

Relationship between the extended, non-nucleosomal intranucleolar chromatin in situ and ribosomal RNA synthesis

Exp. Cell Res.

(1983)

M. Dosil et al.

Functional characterization of Pwp2, a WD family protein essential for the assembly of the 90 S pre-ribosomal particle

J. Biol. Chem.

(2004)

S. Fakan et al.

Localisation of rapidly and slowly labelled nuclear RNA as visualized by high resolution autoradiography

Exp. Cell Res.

(1971)

S. Ferreira-Cerca et al.

Roles of eukaryotic ribosomal proteins in maturation and transport of pre-18S rRNA and ribosome function

Mol. Cell

(2005)

S. Ferreira-Cerca et al.

Analysis of the in vivo assembly pathway of eukaryotic 40S ribosomal proteins

Mol. Cell

(2007)

J. Frank et al.

Multivariate statistical analysis of ribosome electron micrographs. L and R lateral views of the 40 S subunit from HeLa cells

J. Mol. Biol.

(1982)

M. Fromont-Racine et al.

Ribosome assembly in eukaryotes

Gene

(2003)

S.J. Gallagher et al.

Int. J. Biochem. Cell Biol.

(2006)

N. Granboulan et al.

Ultrastructure cytochemistry of the nucleolus. II. Study of the sites of RNA synthesis in the nucleolus and the nucleus

Exp. Cell. Res.

(1965)

P. Grandi et al.

90S pre-ribosomes include the 35S pre-rRNA, the U3 snoRNP, and 40S subunit processing factors but predominantly lack 60S synthesis factors

Mol. Cell

(2002)

S. Granneman et al.

Ribosome biogenesis: of knobs and RNA processing

Exp. Cell Res.

(2004)

S. Granneman et al.

Crosstalk in gene expression: coupling and co-regulation of rDNA transcription, pre-ribosome assembly and pre-rRNA processing

Curr. Opin. Cell Biol.

(2005)

P. Harnpicharnchai et al.

Composition and functional characterization of yeast 66S ribosome assembly intermediates

Mol. Cell

(2001)

P. Hozák

Catching RNA polymerase I in Flagranti: ribosomal genes are transcribed in the dense fibrillar component of the nucleolus

Exp. Cell Res.

(1995)

M.A. Amin et al.

Depletion of nucleophosmin leads to distortion of nucleolar and nuclear structures in HeLa cells

Biochem. J.

(2008)

J.S. Andersen et al.

Nucleolar proteome dynamics

Nature

(2005)

N. Angelier et al.

Tracking the interactions of rRNA processing proteins during nucleolar assembly in living cells

Mol. Biol. Cell

(2005)

J. Bassler et al.

Identification of a 60S pre-ribosomal particle that is closely linked to nuclear export

Mol. Cell

(2001)

A.M. Becam et al.

Ria1p (Ynl163c), a protein similar to elongation factors 2, is involved in the biogenesis of the 60S subunit of the ribosome in Saccharomyces cerevisiae

J. Mol. Genet. Genomics

(2001)

P. Bell et al.

Prenucleolar bodies contain coilin and are assembled in Xenopus egg extract depleted of specific nucleolar proteins and U3 RNA

J. Cell Sci.

(1997)

P. Bell et al.

In vitro assembly of prenucleolar bodies in Xenopus egg extract

J. Cell Biol.

(1992)

M. Biggiogera et al.

Heterogeneous ectopic RNP-derived structures (HERDS) are markers of transcriptional arrest

FASEB J.

(2000)

M. Biggiogera et al.

Immunoelectron microscopical visualization of ribonucleoproteins in the chromatoid body of mouse spermatids

Mol. Reprod. Develop.

(1990)

M. Biggiogera et al.

Nuclear ribonucleoprotein-containing structures undergo severe rearrangement during spontaneous thymocyte apoptosis. A morphological study by electron microscopy

Histochem. Cell Biol.

(1997)

M. Biggiogera et al.

Terminal differentiation of erythroblasts leads to RNP segregation and formation of heterogeneous ectopic RNP-derived structures

Histochem. Cell Biol.

(1999)

M. Biggiogera et al.

Revealing the unseen: the organizer region of the nucleolus

J. Cell Sci.

(2001)

A.V. Borovjagin et al.

Xenopus U3 snoRNA GAC-Box A0 and Box A sequences play distinct functional roles in rRNA processing

Mol. Cell. Biol.

(2001)

K. Boudonck et al.

The movement of coiled bodies visualized in living plant cells by the green fluorescent protein

Mol. Biol. Cell

(1999)

J.W. Brown et al.

The role of the plant nucleolus in pre-mRNA processing

Curr. Top. Microbiol. Immunol.

(2008)

M. Bubunenko et al.

30S ribosomal subunits can be assembled in vivo without primary binding ribosomal protein S15

RNA

(2006)

S. Caldarola et al.

Synthesis and function of ribosomal proteins–fading models and new perspectives

FEBS J.

(2009)

R.S. Cameron et al.

Myosin16b: the COOH-tail region directs localization to the nucleus and overexpression delays S-phase progression

Cell Motil. Cytoskeleton

(2007)

S. Cardinale et al.

Subnuclear localization and dynamics of the pre-mRNA 3′ end processing factor mammalian cleavage factor I 68-kDa subunit

Mol. Biol. Cell

(2007)

A.H. Cavanaugh et al.

Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product

Nature

(1995)

Cited by (40)

Regulation: mTOR and its substrates
2021, Encyclopedia of Biological Chemistry: Third Edition
Mechanistic (or mammalian) target of rapamycin (mTOR) is a master regulator hub that governs versatile cellular signaling networks to regulate a wide range of anabolic and catabolic processes. There are two distinct mTOR complexes, mTORC1 and mTORC2, which are both protein kinases, but contain different ancillary proteins, have distinct substrates and are regulated in different ways.
Here, we summarize current understanding of the control of mTORC1 and mTORC2, and of their substrates, which play key roles in cellular regulation. Through its substrates, mTORC1 promotes anabolic processes that contribute to cell growth, while mTORC2 regulates other protein kinases which have diverse roles in cell function.
Dynamic changes to the skeletal muscle proteome and ubiquitinome induced by the E3 ligase, ASB2β
2021, Molecular and Cellular Proteomics
Citation Excerpt :
Furthermore, as expected, the dSOCS ASB2β mutant was associated with a reduced number of different proteins than the WT complex; however, it was still associated with both cytoplasmic and nuclear proteins, including those in biological processes such as RNA splicing and processing (Fig. 8E). The enrichment of ribosomal proteins with dSOCS ASB2β (and WT ASB2β) suggests that ASB2β may be associated with ribosomes in the cytoplasm and/or in the nucleolus, where ribosomes are assembled (117). Furthermore, the essential absence of mitochondrial proteins associated with dSOCS ASB2β suggests that the downregulation of mitochondrial proteins with increased ASB2β expression in vivo is not due to ASB2β per se, but to other mechanisms secondary to ASB2β.
Ubiquitination is a posttranslational protein modification that has been shown to have a range of effects, including regulation of protein function, interaction, localization, and degradation. We have previously shown that the muscle-specific ubiquitin E3 ligase, ASB2β, is downregulated in models of muscle growth and that overexpression ASB2β is sufficient to induce muscle atrophy. To gain insight into the effects of increased ASB2β expression on skeletal muscle mass and function, we used liquid chromatography coupled to tandem mass spectrometry to investigate ASB2β-mediated changes to the skeletal muscle proteome and ubiquitinome, via a parallel analysis of remnant diGly-modified peptides. The results show that viral vector-mediated ASB2β overexpression in murine muscles causes progressive muscle atrophy and impairment of force-producing capacity, while ASB2β knockdown induces mild muscle hypertrophy. ASB2β-induced muscle atrophy and dysfunction were associated with the early downregulation of mitochondrial and contractile protein abundance and the upregulation of proteins involved in proteasome-mediated protein degradation (including other E3 ligases), protein synthesis, and the cytoskeleton/sarcomere. The overexpression ASB2β also resulted in marked changes in protein ubiquitination; however, there was no simple relationship between changes in ubiquitination status and protein abundance. To investigate proteins that interact with ASB2β and, therefore, potential ASB2β targets, Flag-tagged wild-type ASB2β, and a mutant ASB2β lacking the C-terminal SOCS box domain (dSOCS) were immunoprecipitated from C2C12 myotubes and subjected to label-free proteomic analysis to determine the ASB2β interactome. ASB2β was found to interact with a range of cytoskeletal and nuclear proteins. When combined with the in vivo ubiquitinomic data, our studies have identified novel putative ASB2β target substrates that warrant further investigation. These findings provide novel insight into the complexity of proteome and ubiquitinome changes that occur during E3 ligase-mediated skeletal muscle atrophy and dysfunction.
DEAD-Box Helicase 18 Counteracts PRC2 to Safeguard Ribosomal DNA in Pluripotency Regulation
2020, Cell Reports
Citation Excerpt :
The nucleolus is best known as the site of rRNA transcription and ribosome biogenesis, in which >200 proteins coordinate to synthesize and process rRNAs, and then assemble those rRNAs with the ribosomal proteins. The nucleolus comprises three principal functional components known as the fibrillar center (FC, innermost), the dense fibrillar component (DFC, intermediate), and the granular compartment (GC, outermost), in which transcription of the rDNA, rRNA processing, and ribosome assembly occur, respectively (Cisterna and Biggiogera, 2010). Human and mouse genomes comprise 200–300 copies of ribosomal DNA (rDNA) genes that are clustered in tandem repeats on the short arms of up to 6 acrocentric chromosomes (McStay, 2016).
Embryonic stem cells (ESCs) exhibit high levels of ribosomal RNA (rRNA) transcription and ribosome biogenesis. Here, we reveal an unexpected role for an essential DEAD-box helicase, DDX18, in antagonizing the polycomb repressive complex 2 (PRC2) to prevent deposition of the repressive H3K27me3 mark onto rDNA in pluripotent cells. DDX18 binds and sequesters PRC2 in the outer layer of the nucleolus and counteracts PRC2 complex formation in vivo and in vitro. DDX18 knockdown leads to increased occupancy of PRC2 and H3K27me3 at rDNA loci, accompanied by drastically decreased rRNA transcription and reduced ribosomal protein expression and translation. Auxin-induced rapid degradation of DDX18 enhances PRC2 binding at rDNA. The inhibition of PRC2 partially rescues the effects of DDX18 depletion on rRNA transcription and ESC self-renewal. These results demonstrate a critical role for DDX18 in safeguarding the chromatin and transcriptional integrity of rDNA by counteracting the epigenetic silencing machinery to promote pluripotency.
Effects of mild ozonisation on gene expression and nuclear domains organization in vitro
2017, Toxicology in Vitro
In the last two decades, the use of ozone (O₃) as a complementary medical approach has progressively been increasing; however, its application is still limited due to the numerous doubts about its possible toxicity, despite the low concentrations used in therapy. For an appropriate and safe clinical application of a potentially toxic agent such as O₃, it is crucial to elucidate the cellular response to its administration. Molecular analyses and transmission electron microscopy were here combined to investigate in vitro the effects of O₃ administration on transcriptional activity and nuclear domains organization of cultured SH-SY5Y neuronal cells; low O₃ concentrations were used as those currently administered in clinical practice. Mild ozonisation did not affect cell proliferation or death, while molecular analyses showed an O₃-induced modulation of some genes involved in the cell response to stress (HMOX1, ERCC4, CDKN1A) and in the transcription machinery (CTDSP1). Ultrastructural cytochemistry after experiments of bromouridine incorporation consistently demonstrated an increased transcriptional rate at both the nucleoplasmic (mRNA) and the nucleolar (rRNA) level. No ultrastructural alteration of nuclear domains was observed.
Our molecular, ultrastructural and cytochemical data demonstrate that a mild toxic stimulus such as mild ozonisation stimulate cell protective pathways and nuclear transcription, without altering cell viability. This could possibly account for the positive effects observed in ozone-treated patients.
Astrocyte elevated gene-1 (AEG-1) and the A(E)Ging HIV/AIDS-HAND
2017, Progress in Neurobiology
Citation Excerpt :
AEG-1 translocation to the astrocyte nuclear pockets and colocalization with nucleolar protein fibrillarin, upon oxidative or physical stress such as injury is an important finding highlighting the yet unknown nucleolar function of AEG-1. The main function of the nucleolus is the transcription of ribosomal RNA and synthesis of small and large ribosome subunits (Cisterna and Biggiogera, 2010; Hernandez-Verdun et al., 2010), a tightly regulated process to achieve proper cellular proliferation and cell growth. AEG-1 colocalization with fibrillarin, a dense fibrillar component of the nucleolus participating in ribosome synthesis (Ochs et al., 1985), indicates that AEG-1 may play a role in pre-ribosomal RNA processing in response to oxidative stress, a hallmark of many neuroinflammatory and neurodegenerative disorders including biological aging.
Recent attempts to analyze human immunodeficiency virus (HIV)-1-induced gene expression changes in astrocytes uncovered a multifunctional oncogene, astrocyte elevated gene-1 (AEG-1). Our previous studies revealed that AEG-1 regulates reactive astrocytes proliferation, migration and inflammation, hallmarks of aging and CNS injury. Moreover, the involvement of AEG-1 in neurodegenerative disorders, such as Huntington’s disease and migraine, and its induction in the aged brain suggest a plausible role in regulating overall CNS homeostasis and aging. Therefore, it is important to investigate AEG-1 specifically in aging-associated cognitive decline. In this study, we decipher the common mechanistic links in cancer, aging and HIV-1-associated neurocognitive disorders that likely contribute to AEG-1-based regulation of astrocyte responses and function. Despite AEG-1 incorporation into HIV-1 virions and its induction by HIV-1, tumor necrosis factor-α and interleukin-1β, the specific role(s) of AEG-1 in astrocyte-driven HIV-1 neuropathogenesis are incompletely defined. We propose that AEG-1 plays a central role in a multitude of cellular stress responses involving mitochondria, endoplasmic reticulum and the nucleolus. It is thus important to further investigate AEG-1-based cellular and molecular regulation in order to successfully develop better therapeutic approaches that target AEG-1 to combat cancer, HIV-1 and aging.
Ribosome biogenesis and cancer
2017, Acta Histochemica
Citation Excerpt :
Ribosomal genes are present in the fibrillar components and the newly synthesized rRNA molecules are located in the dense fibrillar component: there they begin their maturation which continues in the granular component, to form ribosome subunits that will be exported to the cytoplasm. In the fibrillar components of the nucleolus, other than rDNA, all the substances necessary for rRNA transcription process are present (Cisterna and Biggiogera, 2010; Derenzini et al., 1990, 2006; Hernandez-Verdun et al., 2010; Ploton et al., 2004; Raska et al., 2006). Therefore these nucleolar components are the structural functional units of the nucleolus (Sirri et al., 2008).
There is growing evidence indicating that the human pathological conditions characterized by an up-regulated ribosome biogenesis are at an increased risk of cancer onset. At the basis of this relationship is the close interconnection between the ribosome biogenesis and cell proliferation. Cell proliferation-stimulating factors also stimulate ribosome production, while the ribosome biogenesis rate controls the cell cycle progression. The major tumour suppressor, the p53 protein, plays an important balancing role between the ribosome biogenesis rate and the cell progression through the cell cycle phases. The perturbation of ribosome biogenesis stabilizes and activates p53, with a consequent cell cycle arrest and/or apoptotic cell death, whereas an up-regulated ribosome production down-regulates p53 expression and activity, thus facilitating neoplastic transformation.
In the present review we describe the interconnection between ribosome biogenesis and cell proliferation, while highlighting the mechanisms by which quantitative changes in ribosome biogenesis may induce cancer.

View all citing articles on Scopus

View full text

Chapter Two - Ribosome Biogenesis: From Structure to Dynamics

Abstract

Introduction

Section snippets

Morphology and cytochemistry

Extra situm

Ribosome Dynamics

Concluding Remarks

Acknowledgments

Exp. Cell Res.

Curr. Biol.

J. Biol. Chem.

J. Ultrastruct. Res.

Exp. Cell Res.

Exp. Cell Res.

Biol. Cell

Methods Cell Biol.

Mol. Cell

Mol. Cell

J. Mol. Biol.

J. Struct. Biol.

Curr. Biol.

Exp. Cell Res.

Biochim. Biophys. Acta

Int. Rev. Exp. Pathol.

Exp. Cell Res.

J. Biol. Chem.

Exp. Cell Res.

Mol. Cell

Mol. Cell

J. Mol. Biol.

Gene

Int. J. Biochem. Cell Biol.

Exp. Cell. Res.

Mol. Cell

Exp. Cell Res.

Curr. Opin. Cell Biol.

Mol. Cell

Exp. Cell Res.

Depletion of nucleophosmin leads to distortion of nucleolar and nuclear structures in HeLa cells

Biochem. J.

Nucleolar proteome dynamics

Nature

Tracking the interactions of rRNA processing proteins during nucleolar assembly in living cells

Mol. Biol. Cell

Identification of a 60S pre-ribosomal particle that is closely linked to nuclear export

Mol. Cell

Ria1p (Ynl163c), a protein similar to elongation factors 2, is involved in the biogenesis of the 60S subunit of the ribosome in Saccharomyces cerevisiae

J. Mol. Genet. Genomics

Prenucleolar bodies contain coilin and are assembled in Xenopus egg extract depleted of specific nucleolar proteins and U3 RNA

J. Cell Sci.

In vitro assembly of prenucleolar bodies in Xenopus egg extract

J. Cell Biol.

Heterogeneous ectopic RNP-derived structures (HERDS) are markers of transcriptional arrest

FASEB J.

Immunoelectron microscopical visualization of ribonucleoproteins in the chromatoid body of mouse spermatids

Mol. Reprod. Develop.

Nuclear ribonucleoprotein-containing structures undergo severe rearrangement during spontaneous thymocyte apoptosis. A morphological study by electron microscopy

Histochem. Cell Biol.

Terminal differentiation of erythroblasts leads to RNP segregation and formation of heterogeneous ectopic RNP-derived structures

Histochem. Cell Biol.

Revealing the unseen: the organizer region of the nucleolus

J. Cell Sci.

Xenopus U3 snoRNA GAC-Box A0 and Box A sequences play distinct functional roles in rRNA processing

Mol. Cell. Biol.

The movement of coiled bodies visualized in living plant cells by the green fluorescent protein

Mol. Biol. Cell

The role of the plant nucleolus in pre-mRNA processing

Curr. Top. Microbiol. Immunol.

30S ribosomal subunits can be assembled in vivo without primary binding ribosomal protein S15

RNA

Synthesis and function of ribosomal proteins–fading models and new perspectives

FEBS J.

Myosin16b: the COOH-tail region directs localization to the nucleus and overexpression delays S-phase progression

Cell Motil. Cytoskeleton

Subnuclear localization and dynamics of the pre-mRNA 3′ end processing factor mammalian cleavage factor I 68-kDa subunit

Mol. Biol. Cell

Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product

Nature