Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export.
Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export.
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DOI：
10.1093/nar/gkv1058
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发表时间：
2015-11-16
影响因子：
14.9
通讯作者：
Noegel AA
中科院分区：
文献类型：
--
作者：
Li P;Noegel AA
通过核孔复合物（NPC）的信使核糖核蛋白（mRNP）的核输出可大致分为两种形式：批量输出和特异性输出，分别涉及核RNA输出因子1（NXF1）依赖性途径和染色体区域维持1（CRM1）依赖性途径。 SUN 蛋白构成核骨架和细胞骨架连接体 (LINC) 复合物的内核被膜成分。在这里，我们表明哺乳动物细胞需要 SUN1 才能有效地输出核 mRNP。结果表明，SUN1 和 SUN2 均与异质核核糖核蛋白 (hnRNP) F/H 和 hnRNP K/J 相互作用。 SUN1 耗尽会抑制 mRNA 输出，导致 hnRNP 和 Poly(A)+RNA 在细胞核中积累。 Leptomycin B 处理表明 SUN1 在哺乳动物 mRNA 输出中发挥作用，涉及 NXF1 依赖性途径。 SUN1 通过与 NXF1 的直接相互作用与 mRNP 复合物结合来介导 mRNA 输出。此外，SUN1 通过与 Nup153（参与 mRNA 输出的核孔成分）直接相互作用与 NPC 结合。综上所述，我们的结果表明，内核包膜蛋白 SUN1 除了作为 LINC 复合物的核心成分外，还具有其他功能，并且它是哺乳动物 mRNA 输出途径的一个组成部分，这表明 SUN1 将含有 NXF1 的 mRNP 招募到核膜上并将其移交给 Nup153 的模型。
Nuclear export of messenger ribonucleoproteins (mRNPs) through the nuclear pore complex (NPC) can be roughly classified into two forms: bulk and specific export, involving an nuclear RNA export factor 1 (NXF1)-dependent pathway and chromosome region maintenance 1 (CRM1)-dependent pathway, respectively. SUN proteins constitute the inner nuclear envelope component of the linker of nucleoskeleton and cytoskeleton (LINC) complex. Here, we show that mammalian cells require SUN1 for efficient nuclear mRNP export. The results indicate that both SUN1 and SUN2 interact with heterogeneous nuclear ribonucleoprotein (hnRNP) F/H and hnRNP K/J. SUN1 depletion inhibits the mRNP export, with accumulations of both hnRNPs and poly(A)+RNA in the nucleus. Leptomycin B treatment indicates that SUN1 functions in mammalian mRNA export involving the NXF1-dependent pathway. SUN1 mediates mRNA export through its association with mRNP complexes via a direct interaction with NXF1. Additionally, SUN1 associates with the NPC through a direct interaction with Nup153, a nuclear pore component involved in mRNA export. Taken together, our results reveal that the inner nuclear envelope protein SUN1 has additional functions aside from being a central component of the LINC complex and that it is an integral component of the mammalian mRNA export pathway suggesting a model whereby SUN1 recruits NXF1-containing mRNP onto the nuclear envelope and hands it over to Nup153.