Cajal bodies in neurons

Lafarga, Miguel; Tapia, Olga; Romero, Ana; Berciano, Marı́a T.

doi:10.1080/15476286.2016.1231360

Cited by 45 publications

(38 citation statements)

References 96 publications

(158 reference statements)

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“…4A ). Similarly, gems, SMN-positive and coilin-negative nuclear bodies 43 , 44 , were never observed in SMN∆7 MNs, and SMN was not concentrated in PARGs (Fig. 4B ).…”

Section: Resultsmentioning

confidence: 73%

“…To establish the identity of the PARG as a distinct nuclear structure in SMA MNs, we performed double labeling for poly(A) RNA in combination with molecular markers of nuclear compartments, such as coilin (Cajal bodies), SMN (gems), the TMG-cap (nuclear speckles) and the proteasome 20S (clastosomes). In a recent study, we demonstrated that the reduced levels of SMN in MNs from SMN∆7 mice were associated with a severe depletion of Cajal bodies 34 , nuclear structures involved in the biogenesis of both spliceosomal snRNPs and nucleolar snoRNPs (for a review, see 42 , 43 . Co-staining for poly(A) RNA and coilin confirmed the depletion of typical Cajal bodies in SMN∆7 MNs.…”

Section: Resultsmentioning

confidence: 99%

“…Although we have previously reported the presence of PARGs in sensory ganglion neurons upon proteasome inhibition 16 , 17 , the present work provides the first demonstration that these structures are present in SMA MNs. The PARG represents a distinct nuclear entity that is clearly distinguishable by its structure and molecular composition from other nuclear compartments, such as nuclear speckles 9 , Cajal bodies 43 , 59 , 60 , gems 44 and clastosomes 45 . PARGs share with nuclear speckles the presence of poly(A) RNAs; however, PARGs lack spliceosomal snRNPs and display an ultrastructural configuration as sharply defined nuclear bodies that is clearly different from the interchromatin granule clusters of nuclear speckles 9 , 43 .…”

Section: Discussionmentioning

confidence: 99%

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Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNΔ7 mouse model of SMA

Narcís

Tapia

Tarabal

et al. 2018

Sci Rep

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Spinal muscular atrophy (SMA) is a severe motor neuron (MN) disease caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene, which results in reduced levels of the SMN protein and the selective degeneration of lower MNs. The best-known function of SMN is the biogenesis of spliceosomal snRNPs, the major components of the pre-mRNA splicing machinery. Therefore, SMN deficiency in SMA leads to widespread splicing abnormalities. We used the SMN∆7 mouse model of SMA to investigate the cellular reorganization of polyadenylated mRNAs associated with the splicing dysfunction in MNs. We demonstrate that SMN deficiency induced the abnormal nuclear accumulation in euchromatin domains of poly(A) RNA granules (PARGs) enriched in the splicing regulator Sam68. However, these granules lacked other RNA-binding proteins, such as TDP43, PABPN1, hnRNPA12B, REF and Y14, which are essential for mRNA processing and nuclear export. These effects were accompanied by changes in the alternative splicing of the Sam68-dependent Bcl-x and Nrnx1 genes, as well as changes in the relative accumulation of the intron-containing Chat, Chodl, Myh9 and Myh14 mRNAs, which are all important for MN functions. PARG-containing MNs were observed at presymptomatic SMA stage, increasing their number during the symptomatic stage. Moreover, the massive accumulations of poly(A) RNA granules in MNs was accompanied by the cytoplasmic depletion of polyadenylated mRNAs for their translation. We suggest that the SMN-dependent abnormal accumulation of polyadenylated mRNAs and Sam68 in PARGs reflects a severe dysfunction of both mRNA processing and translation, which could contribute to SMA pathogenesis.

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“…4A ). Similarly, gems, SMN-positive and coilin-negative nuclear bodies 43 , 44 , were never observed in SMN∆7 MNs, and SMN was not concentrated in PARGs (Fig. 4B ).…”

Section: Resultsmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNΔ7 mouse model of SMA

Narcís

Tapia

Tarabal

et al. 2018

Sci Rep

Self Cite

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“…In result, we describe dynamic regulation of several previously undescribed pathways in response to environmental stimulation. As such, we see regulation of RNA-processing non-coding RNAs, several of which are found in subnuclear Cajal bodies, that are particularly prominent in neurons - especially, when transcriptionally active - and are crucially involved in splicing regulation ( Wang et al, 2016 ; Lafarga et al, 2017 ). Our RNA-seq experiment thus offers exclusive and comprehensive insight into gene regulation in response to a social stimulus in the amygdala.…”

Section: Discussionmentioning

confidence: 99%

Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice

Stilling

Moloney

Ryan

et al. 2018

eLife

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Social behaviour is regulated by activity of host-associated microbiota across multiple species. However, the molecular mechanisms mediating this relationship remain elusive. We therefore determined the dynamic, stimulus-dependent transcriptional regulation of germ-free (GF) and GF mice colonised post weaning (exGF) in the amygdala, a brain region critically involved in regulating social interaction. In GF mice the dynamic response seen in controls was attenuated and replaced by a marked increase in expression of splicing factors and alternative exon usage in GF mice upon stimulation, which was even more pronounced in exGF mice. In conclusion, we demonstrate a molecular basis for how the host microbiome is crucial for a normal behavioural response during social interaction. Our data further suggest that social behaviour is correlated with the gene-expression response in the amygdala, established during neurodevelopment as a result of host-microbe interactions. Our findings may help toward understanding neurodevelopmental events leading to social behaviour dysregulation, such as those found in autism spectrum disorders (ASDs).

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“…This complex plays a role in trafficking of telomerase and small Cajal body (CB) RNAs through the proper folding of the telomerase cofactor, TCAB1 [52]. CBs are transcription-dependent nuclear compartments and play a critical role in neuron biology through snRNP and snoRNP assembly [53]. Interestingly, Coyaud et al [20] demonstrated that ZIKV NS5 expression leads to an increase in the absolute number of CBs per cell, but to a reduction of the volume of these CBs, suggesting that NS5 expression could lead to CB fragmentation.…”

Section: Discussionmentioning

confidence: 99%

Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins

Golubeva

Nepomuceno

Gregoriis

et al. 2020

Cells

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The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding, or perinatal exposure. After the 2015–2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins, leading to microcephaly. Here, we present a systematic annotation of interactions between human proteins and the seven non-structural ZIKV proteins corresponding to a Brazilian isolate. The interaction network was generated by combining tandem-affinity purification followed by mass spectrometry with yeast two-hybrid screens. We identified 150 human proteins, involved in distinct biological processes, as interactors to ZIKV non-structural proteins. Our interacting network is composed of proteins that have been previously associated with microcephaly in human genetic disorders and/or animal models. Further, we show that the protein inhibitor of activated STAT1 (PIAS1) interacts with NS5 and modulates its stability. This study builds on previously published interacting networks of ZIKV and genes related to autosomal recessive primary microcephaly to generate a catalog of human cellular targets of ZIKV proteins implicated in processes related to microcephaly in humans. Collectively, these data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs that may disrupt the interaction and reduce the health damage to the fetus.

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Cajal bodies in neurons

Cited by 45 publications

References 96 publications

Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNΔ7 mouse model of SMA

Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNΔ7 mouse model of SMA

Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice

Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins

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