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Nucleic Acids Res. 2017 May 19;45(9):5399-5413. doi: 10.1093/nar/gkx031.

SECIS-binding protein 2 interacts with the SMN complex and the methylosome for selenoprotein mRNP assembly and translation.

Author information

1
Université de Strasbourg, Centre National de la Recherche Scientifique, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire, F-67000 Strasbourg, France.
2
Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine, Centre National de la Recherche Scientifique, UMR 7365, Faculté de Médecine, 54506 Vandoeuvre-les-Nancy Cedex, France.
3
Département de Biologie Structurale Intégrative, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS UMR7104, INSERM U964, 67404 Illkirch, France.
4
Université Pierre et Marie Curie, UMRS 974, INSERM, FRE3617, Institut de Myologie, 75013 Paris, France.

Abstract

Selenoprotein synthesis requires the co-translational recoding of a UGASec codon. This process involves an RNA structural element, called Selenocysteine Insertion Sequence (SECIS) and the SECIS binding protein 2 (SBP2). Several selenoprotein mRNAs undergo unusual cap hypermethylation by the trimethylguanosine synthase 1 (Tgs1), which is recruited by the ubiquitous Survival of MotoNeurons (SMN) protein. SMN, the protein involved in spinal muscular atrophy, is part of a chaperone complex that collaborates with the methylosome for RNP assembly. Here, we analyze the role of individual SMN and methylosome components in selenoprotein mRNP assembly and translation. We show that SBP2 interacts directly with four proteins of the SMN complex and the methylosome core proteins. Nevertheless, SBP2 is not a methylation substrate of the methylosome. We found that both SMN and methylosome complexes are required for efficient translation of the selenoprotein GPx1 in vivo. We establish that the steady-state level of several selenoprotein mRNAs, major regulators of oxidative stress damage in neurons, is specifically reduced in the spinal cord of SMN-deficient mice and that cap hypermethylation of GPx1 mRNA is affected. Altogether we identified a new function of the SMN complex and the methylosome in selenoprotein mRNP assembly and expression.

PMID:
28115638
PMCID:
PMC5605228
DOI:
10.1093/nar/gkx031
[Indexed for MEDLINE]
Free PMC Article

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