Nuclear Bodies: Random Aggregates of Sticky Proteins or Crucibles of Macromolecular Assembly?

Matera, A. Gregory; Izaguire-Sierra, Mario; Praveen, Kavita; Rajendra, T. K.

doi:10.1016/j.devcel.2009.10.017

Cited by 175 publications

(178 citation statements)

References 109 publications

(159 reference statements)

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“…In addition to spliceosomal snRNPs, four other distinct sets of RNA processing machineries-those supporting histone mRNA 3′-end processing, telomere maintenance, rRNA and miRNA processing-are highly enriched in CBs in some cells and organisms 1,7 . However, the histone mRNA 3′-processing machinery is concentrated in a separate, coilin-deficient nuclear body in zebrafish embryos, suggesting that defects in histone expression are unlikely to contribute to the coilin morphant phenotype 30 .…”

Section: Discussionmentioning

confidence: 99%

Section: 3 a R T I C L E Smentioning

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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Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis

Strzelecka

Trowitzsch

Weber

et al. 2010

Nat Struct Mol Biol

150

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: Discussionmentioning

confidence: 99%

Section: 3 a R T I C L E Smentioning

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

150

164

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“…[4][5][6][7] Since that time, the number of known cellular components that are enriched in the Cajal body has been growing. 3,[8][9][10] These components include factors important for the maturation and function of Sm-class small nuclear ribonucleoproteins (snRNPs), core particles of the spliceosome. The colocalization of Cajal bodies with relevant small nuclear RNA (snRNA) gene clusters, RNAs that guide post-transcriptional modification of snRNPs, and snRNP specific proteins provide important clues regarding the functions of Cajal bodies.…”

Section: Cajal Bodies and Their Componentsmentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

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Survival Motor Neuron (SMN) protein localizes to both the nucleus and the cytoplasm. Cytoplasmic SMN is diffusely localized in large oligomeric complexes with core member proteins, called Gemins. Biochemical and cell biological studies have demonstrated that the SMN complex is required for the cytoplasmic assembly and nuclear transport of Sm-class ribonucleoproteins (RNPs). Nuclear SMN accumulates with spliceosomal small nuclear (sn)RNPs in Cajal bodies, sub-domains involved in multiple facets of snRNP maturation. Thus, the SMN complex forms stable associations with both nuclear and cytoplasmic snRNPs, and plays a critical role in their biogenesis. In this review, we focus on potential functions of the nuclear SMN complex, with particular emphasis on its role within the Cajal body.

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“…The mammalian cell nucleus is compartmentalized into multiple non-membranous subnuclear domains such as nucleoli, nuclear speckles, paraspeckles, Cajal bodies and promyelocytic leukemia (PML) bodies, which in turn contain specific groups of proteins and RNAs involved in special nuclear processes [25,26]. With the respective identification of NEAT1 RNA and NEAT2 RNA in paraspeckles and splicing speckles, it has been further suggested that these nuclear-retained lncRNAs could play important function in a variety of gene-regulatory processes observed in multicellular organisms, especially the transcriptional regulation and RNA metabolism [27].…”

Section: Biological Features Of Lncrnasmentioning

confidence: 99%

Long non-coding RNA-guided regulation in organisms

Xu²,

Li³

2013

Sci. China Life Sci.

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It is clear that RNA is more than just a messenger between gene and protein. The mammalian genome is pervasively transcribed, giving rise to tens of thousands of non-coding transcripts. Whether all of these transcripts are functional remains to be elucidated, but it is evident that there are many functional long non-coding RNAs (lncRNAs). Recent studies have set out to decode the regulatory role and functional diversity of lncRNAs. Here we organize these studies to highlight the significant involvements of lncRNAs in regulation of gene expression and human physiological and pathological processes, which are achieved by their interaction with DNA, RNA or protein. lncRNAs, gene expression, physiological and pathological processes, interactionCitation:

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Nuclear Bodies: Random Aggregates of Sticky Proteins or Crucibles of Macromolecular Assembly?

Cited by 175 publications

References 109 publications

Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis

Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis

SMN - A chaperone for nuclear RNP social occasions?

Long non-coding RNA-guided regulation in organisms

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