Role of Acinus in regulating retinoic acid-responsive gene pre-mRNA splicing.
Role of Acinus in regulating retinoic acid-responsive gene pre-mRNA splicing.
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DOI：
10.1002/jcp.24804
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发表时间：
2015-04
影响因子：
5.6
通讯作者：
Soprano, Dianne Robert
中科院分区：
文献类型：
--
作者：
Wang, Fang;Soprano, Kenneth J.;Soprano, Dianne Robert
腺泡-S '是视黄酸受体（RAR）依赖性基因转录的共阻遏物，并已被认为参与RNA加工。在这项研究中，腺泡异构体在调节前mRNA剪接的作用进行了探讨，使用体内剪接测定。Acinus-L和Acinus-S '均能增加含有弱5′剪接位点的视黄酸（RA）应答小基因的剪接，但对含有强5′剪接位点的RA应答小基因的剪接无影响，Acinus-L的活性高于Acinus-S'。RA处理以剂量和时间依赖性方式进一步增强腺泡对弱5′剪接位点的剪接，表明除了不依赖RA的腺泡活性外，还存在RA依赖性活性。使用含有几种不同启动子的小基因构建体时，腺泡的RA非依赖性效应发生不同程度的变化，而腺泡的RA依赖性剪接活性对源自由含有RA响应元件（RARE）的启动子驱动的小基因的转录物具有特异性。这表明腺泡的配体依赖性剪接活性与结合至RARE的RA激活的RAR相关。RRM结构域对于腺泡的RA依赖性剪接活性是必需的，而腺泡的RA非依赖性剪接活性被RNPS 1抑制。重要的是，体内内源性人RARβ和Bcl-x剪接的测量表明，腺泡刺激这两个基因的较弱的选择性5′剪接位点的使用，RARβ以RA依赖的方式，Bcl-x以RA非依赖的方式。综上所述，这些研究表明腺泡在RAR依赖性剪接和RAR依赖性转录中起作用。
Acinus-S’ is a co-repressor for retinoic acid receptor (RAR)-dependent gene transcription and has been suggested to be involved in RNA processing. In this study the role of Acinus isoforms in regulating pre-mRNA splicing was explored using in vivo splicing assays. Both Acinus-L and Acinus-S’, with the activity of Acinus-L higher than that of Acinus-S’, increase the splicing of a retinoic acid (RA)-responsive minigene containing a weak 5′ splice site but not a RA-responsive minigene containing a strong 5′ splice site. RA treatment further enhances the splicing of the weak 5′ splice site by Acinus in a dose- and time-dependent manner, suggesting a RA-dependent activity in addition to a RA-independent activity of Acinus. The RA-independent effect of Acinus occurs to varying degrees using minigene constructs containing several different promoters while the RA-dependent splicing activity of Acinus is specific for transcripts derived from the minigene driven by a RA response element (RARE)-containing promoter. This suggests that the ligand-dependent splicing activity of Acinus is related to the RA-activated RAR bound to the RARE. The RRM domain is necessary for the RA-dependent splicing activity of Acinus and the RA-independent splicing activity of Acinus is repressed by RNPS1. Importantly, measurement of the splicing of endogenous human RARβ and Bcl-x in vivo demonstrates that Acinus stimulates the use of the weaker alternative 5′ splice site of these two genes in a RA-dependent manner for RARβ and a RA-independent manner for Bcl-x. Taken together, these studies demonstrate that Acinus functions in both RAR-dependent splicing and RAR-dependent transcription.
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影响因子：
14.9
作者：
Cartegni, L;Wang, JH;Krainer, AR
通讯作者：
Krainer, AR
影响因子：
4.8
作者：
Jung, DJ;Na, SY;Lee, JW
通讯作者：
Lee, JW
DOI：
10.1073/pnas.1017700108
发表时间：
2011-05-17
影响因子：
11.1
作者：
Cho, Suhyung;Hoang, Amy;Ghosh, Gourisankar
通讯作者：
Ghosh, Gourisankar
影响因子：
5.3
作者：
Alpatov, R;Munguba, GC;Sugrue, SP
通讯作者：
Sugrue, SP
影响因子：
12.4
作者：
Hu, Y.;Liu, Z.;Ye, K.
通讯作者：
Ye, K.