De Novo Formation of a Subnuclear Body

Kaiser, Trish E.; Intine, Robert V.; Dundr, Miroslav

doi:10.1126/science.1165216

Cited by 236 publications

(238 citation statements)

References 25 publications

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“…The number of snRNPcontaining foci per nucleus in the coilin morphants was significantly decreased by a factor of 5 on average (Fig. 2b), consistent with a requirement for coilin in CB integrity 23,24 . Notably, embryos rescued by co-injection with YFP-coilin showed CBs defined by YFP-coilin protein and endogenous snRNPs (Fig.…”

Section: A R T I C L E Ssupporting

confidence: 63%

“…We disrupted morphologically defined CBs in embryos by depleting coilin, a protein that is absolutely required for the assembly and maintenance of the CB 23,24 . Coilin depletion led to reduced cell proliferation, developmental arrest and cell death.…”

Section: Discussionmentioning

confidence: 99%

Section: 3 a R T I C L E Smentioning

confidence: 99%

“…a r t i c l e s in CB assembly 23,24 . The fact that injection of purified human snRNPs bypasses the embryonic requirement for coilin indicates that a deficit in snRNP assembly is the primarily lesion caused by coilin depletion.…”

Section: Mature Human Spliceosomal Snrnps Rescue the Coilin Morphantmentioning

confidence: 99%

“…However, coilin has never been identified as a stable component of any of the macromolecular complexes found in CBs, such as the spliceosomal snRNPs, despite exhaustive biochemical study and characterization by MS 4 . Taken together, this evidence has led to the view that coilin provides the structural scaffold of CBs through self association and a network of low-affinity interactions with CB components 1,5,24,28 .Coilin clearly has a central role in the integrity of the CB, but the functional consequences to cellular or organismal physiology from Spliceosomal small nuclear ribonucleoproteins (snRNPs), comprised of small nuclear RNAs (snRNAs) in complex with snRNPspecific proteins, are essential for pre-mRNA splicing. Coilin is not a snRNP protein but concentrates snRNPs and their assembly intermediates in Cajal bodies (CBs).…”

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confidence: 99%

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Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis

Strzelecka

Trowitzsch

Weber

et al. 2010

Nat Struct Mol Biol

153

164

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0 3 a r t i c l e sIn eukaryotes, organelles delimited by lipid bilayers support the organization of cellular functions, as exemplified by the segregation of chromatin into the cell nucleus. However, many subcellular compartments-nucleoli, Cajal and PML bodies, polar granules, stress granules, P bodies and others-lack membranes. How these structures contribute to cellular physiology is largely unknown 1 . The Cajal body (CB) is a 0.5-to 1-µm nuclear compartment initially described by Ramon y Cajal in silver-stained sections of vertebrate cerebral cortex 2 . Because the CB is conserved in evolution and is uniquely marked by the protein coilin, it has served as a general model for subnuclear structure and function 1,2 . Numerous factors essential for pre-mRNA splicing, histone mRNA 3′-end processing, telomere maintenance and rRNA processing are concentrated in CBs. Yet CB components exchange rapidly with the nucleoplasm, where most of these processes occur 3 . The challenge, therefore, has been to identify the function of CBs.Despite the localization of splicing machinery in CBs, they are not the sites of pre-mRNA splicing 4,5 . Splicing occurs throughout the nucleus and is catalyzed by the spliceosome, a macromolecular complex formed on pre-mRNA from five essential snRNPs 6 . Each spliceosomal snRNP comprises a unique 100-to 200-nucleotide snRNA (U1, U2, U4, U5 and U6) that is post-transcriptionally modified and associated with a number of snRNP-specific proteins 6,7 . Several roles for CBs in spliceosomal snRNP biogenesis have been proposed based on the localization of specific steps in snRNP assembly in the CBs of cultured cell lines. After transcription and export to the cytoplasm, U1, U2, U4 and U5 snRNAs receive a heteroheptameric ring of Sm proteins assembled by the SMN complex; subsequently, their 5′ ends are hypermethylated 8 . The Sm ring and trimethylguanosine (TMG) cap are signals for snRNP reimport into the nucleus, where these still-immature core snRNPs first concentrate in CBs 9-12 . CBs contain scaRNAs, which then guide site-specific modification of the snRNAs 13 . Importantly, intermediates in the final snRNP maturation steps, reflecting RNA structural rearrangements and the recruitment of snRNP-specific proteins, are highly concentrated in CBs 14-17 . These observations have led to the proposal that CBs are the sites of snRNP assembly, but an essential role for CBs in this process has not been shown.The coilin protein may hold the key to CB function. Immunoelectron microscopy studies of CBs reveal thread-like, coilin-positive aggregates, suggesting that coilin is integral to CB structure 2 . Consistent with this, coilin resides longer in CBs than any other examined component in vivo 3,18 . Notably, depletion of coilin results in the dispersal of many CB components. Without coilin, spliceosomal factors become nucleoplasmic, and other classes of CB-localized factors (for example, SMN, fibrillarin and small Cajal body-specific RNAs (scaRNAs)) continue to self-associate in discrete 'residual bodies' ...

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Section: A R T I C L E Ssupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: 3 a R T I C L E Smentioning

confidence: 99%

Section: Mature Human Spliceosomal Snrnps Rescue the Coilin Morphantmentioning

confidence: 99%

mentioning

confidence: 99%

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Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis

Strzelecka

Trowitzsch

Weber

et al. 2010

Nat Struct Mol Biol

153

164

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Nucleolus

Shaw

2010

Encyclopedia of Life Sciences

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The nucleolus is a nuclear substructure where the genes for three of the four ribosomal ribonucleic acids (RNAs) are transcribed and where ribosomal subunits are assembled. Although the nucleolus has been intensively studied for many years, recent progress has been very rapid. We are beginning to understand how the biochemical processes carried out in the nucleolus relate to the observable structure. There is much emerging evidence that the nucleolus is also involved in many other roles, particularly in the biogenesis of RNA‐containing complexes, in stress sensing and in the control of cellular activity and proliferation. Recent observations of nucleolar proteins in living cells have shown that the nucleolus and its components are highly dynamic and that the observed structure is a steady state result of the dynamic diffusion of proteins and other macromolecules throughout the nucleoplasm and nucleolus and their relative residence times in the various locations. Key Concepts: The nucleolus is the clearest subnuclear structure in most eukaryotic cells and is the site of rDNA transcription and ribosome biosynthesis. Most nucleoli show three types of substructural components in standard thin section transmission electron microscopy: fibrillar centres (FC), dense fibrillar component (DFC) and granular component (GC). The interpretation of nucleolar ultrastructure in functional terms is still not fully understood, but rDNA transcription occurs within the DFC, and the subsequent stages of rRNA processing occur vectorially in enveloping layers as the transcripts move away from the transcription sites. Nucleoli share factors and, possibly, processes with other subnuclear structures, particularly Cajal bodies. Most nucleolar proteins are highly dynamic and diffuse freely through the nucleolus and nucleoplasm; ‘nucleolar’ proteins have a residence time in the nucleolus of the order of a few tens of seconds. The nucleolus is involved in many other nonconventional activities such as biogenesis of other RNP complexes, mRNA surveillance, stress sensing and control of cell proliferation.

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Nucleolus

Shaw

2015

Encyclopedia of Life Sciences

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The nucleolus is a nuclear substructure where the genes for three of the four ribosomal ribonucleic acids ( rRNAs ) are transcribed and where ribosomal subunits are assembled. Although the nucleolus has been intensively studied for many years, recent progress has been very rapid. We are beginning to understand how the biochemical processes carried out in the nucleolus relate to the observable structure. Recent observations of nucleolar proteins in living cells have shown that the nucleolus and its components are highly dynamic and that the observed structure is a steady state resulting from the relative nucleolar residence times of the various molecular components. There is much evidence that the nucleolus is also involved in many other roles, particularly in the biogenesis of RNA (ribonucleic acid)‐containing complexes, in stress sensing and in the control of cellular activity and proliferation. There is considerable current interest in the nucleolus and ribosome biogenesis as targets for cancer therapy. Key Concepts The nucleolus is the clearest subnuclear structure in most eukaryotic cells and is the site of rDNA transcription and ribosome biosynthesis. Most nucleoli show three types of substructural components in standard thin section transmission electron microscopy: fibrillar centres (FC), dense fibrillar component (DFC) and granular component (GC). The interpretation of nucleolar ultrastructure in functional terms is still not fully understood, but rDNA transcription occurs within the DFC, and the subsequent stages of rRNA processing occur vectorially in enveloping layers as the transcripts move away from the transcription sites. Nucleoli share factors and, possibly, processes with other subnuclear structures, particularly Cajal bodies. Most nucleolar proteins are highly dynamic and diffuse freely through the nucleolus and nucleoplasm; ‘nucleolar’ proteins have a longer residence time in the nucleolus than in other parts of the nucleus, but these nucleolar residence times are in some cases as short as a few tens of seconds. The nucleolus is involved in many other nonconventional activities such as biogenesis of other RNP complexes, mRNA surveillance, and control of cell proliferation. The nucleolus is involved in stress sensing and has roles in triggering the p53 DNA damage response pathways.

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De Novo Formation of a Subnuclear Body

Cited by 236 publications

References 25 publications

Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis

Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis

Nucleolus

Nucleolus

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