The SAP motif and C-terminal RS- and RD/E-rich region influences the sub-nuclear localization of Acinus isoforms.

The SAP motif and C-terminal RS- and RD/E-rich region influences the sub-nuclear localization of Acinus isoforms.
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DOI:
10.1002/jcb.24893
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发表时间:
2014-12
影响因子:
4
通讯作者:
Soprano, Dianne Robert
Soprano, Dianne Robert
中科院分区:
生物学2区
文献类型:
--
作者:
Wang, Fang;Wendling, Karen S.;Soprano, Kenneth J.;Soprano, Dianne Robert

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据报道,腺泡蛋白在细胞凋亡、RNA加工和基因转录调控中发挥作用,包括RA依赖的转录。腺泡有三种不同的亚型:L、S和S。腺泡的异构体在N-末端不同,而C-末端在所有的异构体中是一致的。用荧光显微镜观察了腺泡-L和腺泡-S的亚核定位。腺泡-S与SC35共定位于核斑点,而腺泡-L则弥漫分布于核质中。RA处理对腺泡-L和腺泡-S的亚核定位影响不大。确定了腺泡-L和腺泡-S‘进行亚核定位所需的结构域/区域。S‘的斑点亚核定位依赖于其C末端的RS-和RD/E富集区,但与该区域内Ser-453和Ser-604的磷酸化状态无关。腺泡-L独特的N端SAP基序负责其在细胞核内的弥漫定位。此外,腺泡异构体的亚核定位是由更强大的SAP基序L和所有腺泡异构体中富含RS和RD/E的C末端区域的组合所决定的。腺泡病毒的富含RS和RD/E的C末端区域介导了腺泡病毒异构体及其相互作用蛋白RNPS1的共定位。综上所述,SAP基序是导致腺泡-L和腺泡-S核定位不同的原因。腺泡-S和腺泡-L核定位的这种差异可能表明这两种异构体具有不同的功能作用。
Acinus has been reported to function in apoptosis, RNA processing and regulation of gene transcription including RA-dependent transcription. There are three different isoforms of Acinus termed Acinus-L, Acinus-S′ and Acinus-S. The isoforms of Acinus differ in their N-terminus while the C-terminus is consistent in all isoforms. The sub-nuclear localization of Acinus-L and Acinus-S′ was determined using fluorescence microscopy. Acinus-S′ colocalizes with SC35 in nuclear speckles while Acinus-L localizes diffusely throughout the nucleoplasm. RA treatment has little effect on the sub-nuclear localization of Acinus-L and Acinus-S′. The domains/regions necessary for the distinct sub-nuclear localization of Acinus-L and Acinus-S′ were identified. The speckled sub-nuclear localization of Acinus-S′ is dependent on its C-terminal RS- and RD/E-rich region but is independent of the phosphorylation status of Ser-453 and Ser-604 within this region. The unique N-terminal SAP-motif of Acinus-L is responsible for its diffuse localization in the nucleus. Moreover, the sub-nuclear localization of Acinus isoforms is affected by each other, which is determined by the combinatorial effect of the more potent SAP motif of Acinus-L and the C-terminal RS- and RD/E-rich region in all Acinus isoforms. The C-terminal RS- and RD/E-rich region of Acinus mediates the colocalization of Acinus isoforms as well as with its interacting protein RNPS1. In conclusion, the SAP motif is responsible for the difference in the nuclear localization between Acinus-L and Acinus-S′. This difference in the nuclear localization of Acinus-S′ and Acinus-L may suggest that these two isoforms have different functional roles.
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