Targeting of U4/U6 small nuclear RNP assembly factor SART3/p110 to Cajal bodies

Staněk, David; Rader, Stephen D.; Klingauf, Mirko; Neugebauer, Karla M.

doi:10.1083/jcb.200210087

Cited by 94 publications

(124 citation statements)

References 72 publications

(134 reference statements)

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“…Could coilin (and CBs) therefore be involved in spliceosome disassembly and/or the recycling of spliceosomal components? In this context, it is noteworthy that one Cajal body protein, hPrp24/SART3/p110, has been implicated in U4/ U6 recycling (Bell et al 2002;Stanek et al 2003). Similarly, SMN and its associated proteins may also help to ensure that the Sm core is properly reformed onto the snRNA following splicing (Matera 1999;Pellizzoni et al 1998).…”

Section: Discussionmentioning

confidence: 99%

The C-terminal domain of coilin interacts with Sm proteins and U snRNPs

Pillai

Azzouz

et al. 2005

Chromosoma

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Coilin is the signature protein of the Cajal body (CB), a nuclear suborganelle involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs). Newly imported Sm-class snRNPs are thought to traffic through CBs before proceeding to their final nuclear destinations. Loss of coilin function in mice leads to significant viability and fertility problems. Coilin interacts directly with the spinal muscular atrophy (SMA) protein via dimethylarginine residues in its C-terminal domain. Although coilin hypomethylation results in delocalization of survival of motor neurons (SMN) from CBs, high concentrations of snRNPs remain within these structures. Thus, CBs appear to be involved in snRNP maturation, but factors that tether snRNPs to CBs have not been described. In this report, we demonstrate that the coilin C-terminal domain binds directly to various Sm and Lsm proteins via their Sm motifs. We show that the region of coilin responsible for this binding activity is separable from that which binds to SMN. Interestingly, U2, U4, U5, and U6 snRNPs interact with the coilin C-terminal domain in a glutathione S-transferase (GST)-pulldown assay, whereas U1 and U7 snRNPs do not. Thus, the ability to interact with free Sm (and Lsm) proteins as well as with intact snRNPs, indicates that coilin and CBs may facilitate the modification of newly formed snRNPs, the regeneration of 'mature' snRNPs, or the reclamation of unassembled snRNP components.

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Section: Discussionmentioning

confidence: 99%

The C-terminal domain of coilin interacts with Sm proteins and U snRNPs

Pillai

Azzouz

et al. 2005

Chromosoma

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“…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' [19][20][21][22][23] . Moreover, tethering of coilin to a particular nuclear site induces formation of a CB at that site 24 .…”

Section: 3 a R T I C L E Smentioning

confidence: 99%

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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“…Pollard, The SCRIPPS Research Institute, CA; Yang et al 2001) were used as nucleolar markers. Rabbit anti-SART3 antibodies (Stanek et al 2003) were used as nucleoplasmic markers. The monoclonal anti-vimentin antibody VI-01 (Draberova et al 1986) was kindly provided by Pavel Draber (Institute of Molecular Genetics, AS CR, Prague, Czech Republic).…”

Section: Antibodies Immunofluorescence and Light Microscopymentioning

confidence: 99%