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The Exon Junction Complex factor MLN51 is recruited to mRNA granules during cellular stress
Author(s) -
Tomasetto Catherine L,
Baguet Aurelie,
Degot Sebastien,
Le Hir Herve
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a653-d
Subject(s) - rna binding protein , rna splicing , microbiology and biotechnology , messenger rna , cytoplasm , stress granule , exon , rna , chemistry , spliceosome , biology , gene , genetics , translation (biology)
MLN51 (Metastatic Lymph Node 51) also named Barentsz is a protein overexpressed in breast cancer. We showed that MLN51 is a component of the exon junction complex (EJC). The EJC is a multiprotein complex deposited on mRNAs upstream of exon‐exon junctions as a consequence of splicing. In mammalian cells, this complex is composed by the assembly of at least 9 proteins: Magoh, Y14, RNPS1, SRm160, REF, UAP56, eIF4AIII, MLN51 and Pinin. The assembly pathway of all these components is still unclear, however we showed recently that the minimal stable core EJC is formed by a tetrameric complex composed of eIF4AIII, Magoh, Y14 and MLN51. The EJC influences mRNAs metabolism by acting on mRNA subcellular localization, translational efficiency and nonsense mRNA decay. MLN51 is a multimodular protein including within its N‐terminal half, a conserved module named SELOR (SpEckles LOcalizer and RNA binding) implicated in its localization in speckles, binding with RNA and association with the core EJC complex. All core EJC proteins shuttle between the cytoplasm and the nucleus. At steady state, eIF4AIII, Magoh and Y14 are localized in the nucleus while MLN51 is mainly in the cytoplasm. This suggests that MLN51 might also function in the cytoplasm independently from its association with the EJC. We have studied the localization of MLN51 under conditions where mRNA metabolism is altered including cellular stress. During stress, we showed that MLN51 is recruited to mRNAs storage regions known as stress granules (SGs). These regions are believed to play an important role in the regulation of mRNA metabolism during cellular stress response. The recruitment of MLN51 in SGs is independent from its association with the EJC indicating that MLN51 plays discrete functions in mRNA metabolism.