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DC Field | Value | Language |
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dc.contributor.author | Borg, Rebecca M. | - |
dc.contributor.author | Fenech Salerno, Benji | - |
dc.contributor.author | Vassallo, Neville | - |
dc.contributor.author | Bordonne, Rémy | - |
dc.contributor.author | Cauchi, Ruben J. | - |
dc.date.accessioned | 2022-03-03T13:37:53Z | - |
dc.date.available | 2022-03-03T13:37:53Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Borg, R.M., Salerno, B.F., Vassallo, N., Bordonné, R., & Cauchi, R.J. (2016). Disruption of snRNP biogenesis factors Tgs1 and pICln induces phenotypes that mirror aspects of SMN-Gemins complex perturbation in Drosophila, providing new insights into spinal muscular atrophy. Neurobiology of Disease, 94, 245-258. | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar/handle/123456789/90344 | - |
dc.description.abstract | The neuromuscular disorder, spinal muscular atrophy (SMA), results from insufficient levels of the survival motor neuron (SMN) protein. Together with Gemins 2-8 and Unrip, SMN forms the large macromolecular SMN-Gemins complex, which is known to be indispensable for chaperoning the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). It remains unclear whether disruption of this function is responsible for the selective neuromuscular degeneration in SMA. In the present study, we first show that loss of wmd, the Drosophila Unrip orthologue, has a negative impact on the motor system. However, due to lack of a functional relationship between wmd/Unrip and Gemin3, it is likely that Unrip joined the SMN-Gemins complex only recently in evolution. Second, we uncover that disruption of either Tgs1 or pICln, two cardinal players in snRNP biogenesis, results in viability and motor phenotypes that closely resemble those previously uncovered on loss of the constituent members of the SMN-Gemins complex. Interestingly, overexpression of both factors leads to motor dysfunction in Drosophila, a situation analogous to that of Gemin2. Toxicity is conserved in the yeast S. pombe where pICln overexpression induces a surplus of Sm proteins in the cytoplasm, indicating that a block in snRNP biogenesis is partly responsible for this phenotype. Importantly, we show a strong functional relationship and a physical interaction between Gemin3 and either Tgs1 or pICln. We propose that snRNP biogenesis is the pathway connecting the SMN-Gemins complex to a functional neuromuscular system, and its disturbance most likely leads to the motor dysfunction that is typical in SMA. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier Inc. | en_GB |
dc.rights | info:eu-repo/semantics/restrictedAccess | en_GB |
dc.subject | Straps | en_GB |
dc.subject | Amyotrophic lateral sclerosis | en_GB |
dc.subject | Spinal muscular atrophy | en_GB |
dc.subject | Trimethyltin | en_GB |
dc.title | Disruption of snRNP biogenesis factors Tgs1 and pICln induces phenotypes that mirror aspects of SMN-Gemins complex perturbation in Drosophila, providing new insights into spinal muscular atrophy | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1016/j.nbd.2016.06.015 | - |
dc.publication.title | Neurobiology of Disease | en_GB |
Appears in Collections: | Scholarly Works - FacM&SPB |
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