Nucleolar targeting of coilin is regulated by its hypomethylation state

Tapia, Olga; Bengoechea, Rocío; Berciano, Marı́a T.; Lafarga, Miguel

doi:10.1007/s00412-010-0276-7

Cited by 24 publications

(29 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The efficiency of the siRNA was confirmed by immunoblotting ( (Lemm et al, 2006). This coilin reorganization is consistent with previous studies showing nucleolar accumulations of coilin upon the experimental disruption of CBs (Tapia et al, 2010;Gilder and Hebert, 2011) and with our recent observation that SMN depletion in human motor neurons from SMA patients causes CB loss and nucleolar relocalization of coilin (Tapia et al, 2012).…”

Section: Smn Is a Novel Sumo1 Substratesupporting

confidence: 88%

The SMN Tudor SIM-like domain is key to SmD1 and coilin interactions and to Cajal body biogenesis

Tapia

Lafarga

Bengoechea

et al. 2014

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

Cajal bodies (CBs) are nuclear organelles involved in the maturation of spliceosomal small nuclear ribonucleoproteins (snRNPs). They concentrate coilin, snRNPs and the survival motor neuron protein (SMN). Dysfunction of CB assembly occurs in spinal muscular atrophy (SMA). Here, we demonstrate that SMN is a SUMO1 target that has a small ubiquitin-related modifier (SUMO)-interacting motif (SIM)-like motif in the Tudor domain. The expression of SIM-like mutant constructs abolishes the interaction of SMN with the spliceosomal SmD1 (also known as SNRPD1), severely decreases SMN-coilin interaction and prevents CB assembly. Accordingly, the SMN SIM-like-mediated interactions are important for CB biogenesis and their dysfunction can be involved in SMA pathophysiology.

show abstract

Section: Smn Is a Novel Sumo1 Substratesupporting

confidence: 88%

The SMN Tudor SIM-like domain is key to SmD1 and coilin interactions and to Cajal body biogenesis

Tapia

Lafarga

Bengoechea

et al. 2014

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the cap-like Cajal bodies observed upon Fam118B overexpression were not formed around the nucleolus, suggesting that this morphological change in Cajal bodies might reflect an unknown status of these structures. Nevertheless, previous studies have revealed a close crosstalk between nucleoli and Cajal bodies, because many components shuttle between these two structures, including coilin, fibrillarin and Nopp140 (Isaac et al, 1998;Tapia et al, 2010). In line with these observations, we showed that although residues 190-232 of Fam118B are required for the targeting of Fam118B to Cajal bodies, Fam118B mutants (M2, M4 and M6) without this motif translocate to nucleoli.…”

Section: Discussionsupporting

confidence: 88%

Fam118B, a novel component in Cajal bodies, is required for Cajal body formation, snRNP biogenesis and cell viability

Fong

Tang

et al. 2014

Journal of Cell Science

View full text Add to dashboard Cite

Cajal bodies (CBs) are specialized and dynamic compartments in nucleus that are involved in small nuclear ribonucleoprotein (snRNP) biogenesis. Because of the dynamic and multifunctional roles of CBs, it is of great interest to identify components in CBs to better understand their functions. We performed a genome-wide screen to identify proteins that co-localize with Coilin, the CB marker protein. In this study, we identified and characterized Fam118B as a novel component of CBs. Fam118B is widely expressed in a variety of cell lines derived from various origins. Overexpression of Fam118B changes the canonical morphology of CBs, whereas depletion of Fam118B disrupts the localization of CB components, including Coilin, the survival of motor neuron protein (SMN) and the Sm protein D1 (SmD1). Moreover, depletion ofFam118B reduces splicing capacity and inhibits cell proliferation. In addition, Fam118B associates with Coilin and SMN proteins. Fam118B depletion reduces symmetric dimethylarginine modification of SmD1, which in turn diminishes SMN binding to this Sm protein. Taken together, these data indicate that Fam118B, by regulating SmD1 symmetric dimethylarginine modification, plays an important role in CB formation, snRNP biogenesis and cell viability.

show abstract

“…3b). Some immunogold particles appeared scattered over nucleoplasm, presumably corresponding to the nucleoplasmic pool of coilin (Nizami et al 2010;Tapia et al 2010). In motor neurons of the SMA patient, the immunolabeling was detected in typical CBs (Fig.…”

Section: Resultsmentioning

confidence: 97%

Reorganization of Cajal bodies and nucleolar targeting of coilin in motor neurons of type I spinal muscular atrophy

Tapia

Bengoechea

Palanca

et al. 2012

Histochem Cell Biol

Self Cite

View full text Add to dashboard Cite

Type I spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by loss or mutations of the survival motor neuron 1 (SMN1) gene. The reduction in SMN protein levels in SMA leads to degeneration and death of motor neurons. In this study, we have analyzed the nuclear reorganization of Cajal bodies, PML bodies and nucleoli in type I SMA motor neurons with homozygous deletion of exons 7 and 8 of the SMN1 gene. Western blot analysis is is revealed a marked reduction of SMN levels compared to the control sample. Using a neuronal dissociation procedure to perform a careful immunocytochemical and quantitative analysis of nuclear bodies, we demonstrated a severe decrease in the mean number of Cajal bodies per neuron and in the proportion of motor neurons containing these structures in type I SMA. Moreover, most Cajal bodies fail to recruit SMN and spliceosomal snRNPs, but contain the proteasome activator PA28, a molecular marker associated with the cellular stress response. Neuronal stress in SMA motor neurons also increases PML body number. The existence of chromatolysis and eccentric nuclei in SMA motor neurons correlates with Cajal body disruption and nucleolar relocalization of coil in, a Cajal body marker. Our results indicate that the Cajal body is a pathophysiological target in type I SMA motor neurons. They also suggest the Cajal body-dependent dysfunction of snRNP biogenesis and, therefore, pre-mRNA splicing in these neurons seems to be an essential component for SMA pathogenesis.

show abstract

Nucleolar targeting of coilin is regulated by its hypomethylation state

Cited by 24 publications

References 56 publications

The SMN Tudor SIM-like domain is key to SmD1 and coilin interactions and to Cajal body biogenesis

The SMN Tudor SIM-like domain is key to SmD1 and coilin interactions and to Cajal body biogenesis

Fam118B, a novel component in Cajal bodies, is required for Cajal body formation, snRNP biogenesis and cell viability

Reorganization of Cajal bodies and nucleolar targeting of coilin in motor neurons of type I spinal muscular atrophy

Contact Info

Product

Resources

About