Abstract
SUN1, a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, functions in mammalian mRNA export through the NXF1-dependent pathway. It associates with mRNP complexes by direct interaction with NXF1. It also binds to the NPC through association with the nuclear pore component Nup153, which is involved in mRNA export. The SUN1-NXF1 association is at least partly regulated by a protein kinase C (PKC) which phosphorylates serine 113 (S113) in the N-terminal domain leading to reduced interaction. The phosphorylation appears to be important for the SUN1 function in nuclear mRNA export since GFP-SUN1 carrying a S113A mutation was less efficient in restoring mRNA export after SUN1 knockdown as compared to the wild type protein. By contrast, GFP-SUN1-S113D resembling the phosphorylated state allowed very efficient export of poly(A)+RNA. Furthermore, probing a possible role of the LINC complex component Nesprin-2 in this process we observed impaired mRNA export in Nesprin-2 knockdown cells. This effect might be independent of SUN1 as expression of a GFP tagged SUN-domain deficient SUN1, which no longer can interact with Nesprin-2, did not affect mRNA export.
Highlights
SUN1 is an inner nuclear membrane protein and is a member of the SUN domain containing proteins that are composed of a variable N-terminus facing the nucleoplasm, a transmembrane domain and the C-terminal SUN domain through which they can interact with the KASH domain of KASH domain containing proteins in the perinuclear space
MRNAs need to be properly processed; they associate with proteins such as hnRNPs and SR proteins to form mRNPs which bind to the TREX complex and interact with the export receptor NXF1:NXT1. mRNP/NXF1 recognize nucleoporins with FG-domains at the nuclear pore complex (NPC) which mediate docking at the nucleoplasmic side and translocation through the NPC transport channel and release into the cytoplasm[10, 11]
We studied whether the LINC complex is involved in mRNA export as well and whether it cooperates with SUN1
Summary
SUN1 is an inner nuclear membrane protein and is a member of the SUN domain containing proteins that are composed of a variable N-terminus facing the nucleoplasm, a transmembrane domain and the C-terminal SUN domain through which they can interact with the KASH domain of KASH domain containing proteins in the perinuclear space. The CRM1-dependent pathway is used by rRNAs, snRNAs and a subset of mRNAs, whereas the NXF1-dependent pathway is responsible for export of most mRNAs. For export, mRNAs need to be properly processed; they associate with proteins such as hnRNPs and SR proteins to form mRNPs which bind to the TREX (transcription-export) complex and interact with the export receptor NXF1:NXT1. SUN1 has been identified as interaction partner of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in a biochemical screen, but phosphorylation studies were not carried out[13]. We identified potential phosphorylation sites for protein kinase C (PKC) in the N-terminus of SUN1 and investigated the role of this phosphorylation in SUN1 interactions with different binding partners and in mRNA export. GANP is a subunit of the TREX-2 mRNA export complex and interacts with NXF117 We found this protein in complex with SUN18. We studied whether the LINC complex is involved in mRNA export as well and whether it cooperates with SUN1
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