Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly

Claudia Carissimi, Luciano Saieva, Jennifer Baccon, Pieranna Chiarella, Alessio Maiolica, Alan Sawyer, Juri Rappsilber, Livio Pellizzoni

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The survival motor neuron (SMN) protein is the product of the spinal muscular atrophy disease gene. SMN and Gemin2-7 proteins form a large macromolecular complex that localizes in the cytoplasm as well as in the nucleoplasm and in nuclear Gems. The SMN complex interacts with several additional proteins and likely functions in multiple cellular pathways. In the cytoplasm, a subset of SMN complexes containing unrip and Sm proteins mediates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). Here, by mass spectrometry analysis of SMN complexes purified from HeLa cells, we identified a novel protein that is evolutionarily conserved in metazoans, and we named it Gemin8. Co-immunoprecipitation and immunolocalization experiments demonstrated that Gemin8 is associated with the SMN complex and is localized in the cytoplasm and in the nucleus, where it is highly concentrated in Gems. Gemin8 interacts directly with the Gemin6-Gemin7 heterodimer and, together with unrip, these proteins form a heteromeric subunit of the SMN complex. Gemin8 is also associated with Sm proteins, and Gemin8-containing SMN complexes are competent to carry out snRNP assembly. Importantly, RNA interference experiments indicate that Gemin8 knock-down impairs snRNP assembly, and Gemin8 expression is down-regulated in cells with low levels of SMN. These results demonstrate that Gemin8 is a novel integral component of the SMN complex and extend the repertoire of cellular proteins involved in the pathway of snRNP biogenesis.

Original languageEnglish (US)
Pages (from-to)8126-8134
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number12
DOIs
StatePublished - Mar 24 2006

Fingerprint

SMN Complex Proteins
Small Nuclear Ribonucleoproteins
Motor Neurons
Proteins
Gems
Neurons
Cytoplasm
Macromolecular Substances
Spinal Muscular Atrophy
Muscular Diseases
RNA Interference
Mass spectrometry
HeLa Cells
Immunoprecipitation
Genes
Experiments
Mass Spectrometry
RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Carissimi, C., Saieva, L., Baccon, J., Chiarella, P., Maiolica, A., Sawyer, A., ... Pellizzoni, L. (2006). Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly. Journal of Biological Chemistry, 281(12), 8126-8134. https://doi.org/10.1074/jbc.M512243200
Carissimi, Claudia ; Saieva, Luciano ; Baccon, Jennifer ; Chiarella, Pieranna ; Maiolica, Alessio ; Sawyer, Alan ; Rappsilber, Juri ; Pellizzoni, Livio. / Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 12. pp. 8126-8134.
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abstract = "The survival motor neuron (SMN) protein is the product of the spinal muscular atrophy disease gene. SMN and Gemin2-7 proteins form a large macromolecular complex that localizes in the cytoplasm as well as in the nucleoplasm and in nuclear Gems. The SMN complex interacts with several additional proteins and likely functions in multiple cellular pathways. In the cytoplasm, a subset of SMN complexes containing unrip and Sm proteins mediates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). Here, by mass spectrometry analysis of SMN complexes purified from HeLa cells, we identified a novel protein that is evolutionarily conserved in metazoans, and we named it Gemin8. Co-immunoprecipitation and immunolocalization experiments demonstrated that Gemin8 is associated with the SMN complex and is localized in the cytoplasm and in the nucleus, where it is highly concentrated in Gems. Gemin8 interacts directly with the Gemin6-Gemin7 heterodimer and, together with unrip, these proteins form a heteromeric subunit of the SMN complex. Gemin8 is also associated with Sm proteins, and Gemin8-containing SMN complexes are competent to carry out snRNP assembly. Importantly, RNA interference experiments indicate that Gemin8 knock-down impairs snRNP assembly, and Gemin8 expression is down-regulated in cells with low levels of SMN. These results demonstrate that Gemin8 is a novel integral component of the SMN complex and extend the repertoire of cellular proteins involved in the pathway of snRNP biogenesis.",
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Carissimi, C, Saieva, L, Baccon, J, Chiarella, P, Maiolica, A, Sawyer, A, Rappsilber, J & Pellizzoni, L 2006, 'Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly', Journal of Biological Chemistry, vol. 281, no. 12, pp. 8126-8134. https://doi.org/10.1074/jbc.M512243200

Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly. / Carissimi, Claudia; Saieva, Luciano; Baccon, Jennifer; Chiarella, Pieranna; Maiolica, Alessio; Sawyer, Alan; Rappsilber, Juri; Pellizzoni, Livio.

In: Journal of Biological Chemistry, Vol. 281, No. 12, 24.03.2006, p. 8126-8134.

Research output: Contribution to journalArticle

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T1 - Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly

AU - Carissimi, Claudia

AU - Saieva, Luciano

AU - Baccon, Jennifer

AU - Chiarella, Pieranna

AU - Maiolica, Alessio

AU - Sawyer, Alan

AU - Rappsilber, Juri

AU - Pellizzoni, Livio

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Y1 - 2006/3/24

N2 - The survival motor neuron (SMN) protein is the product of the spinal muscular atrophy disease gene. SMN and Gemin2-7 proteins form a large macromolecular complex that localizes in the cytoplasm as well as in the nucleoplasm and in nuclear Gems. The SMN complex interacts with several additional proteins and likely functions in multiple cellular pathways. In the cytoplasm, a subset of SMN complexes containing unrip and Sm proteins mediates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). Here, by mass spectrometry analysis of SMN complexes purified from HeLa cells, we identified a novel protein that is evolutionarily conserved in metazoans, and we named it Gemin8. Co-immunoprecipitation and immunolocalization experiments demonstrated that Gemin8 is associated with the SMN complex and is localized in the cytoplasm and in the nucleus, where it is highly concentrated in Gems. Gemin8 interacts directly with the Gemin6-Gemin7 heterodimer and, together with unrip, these proteins form a heteromeric subunit of the SMN complex. Gemin8 is also associated with Sm proteins, and Gemin8-containing SMN complexes are competent to carry out snRNP assembly. Importantly, RNA interference experiments indicate that Gemin8 knock-down impairs snRNP assembly, and Gemin8 expression is down-regulated in cells with low levels of SMN. These results demonstrate that Gemin8 is a novel integral component of the SMN complex and extend the repertoire of cellular proteins involved in the pathway of snRNP biogenesis.

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