Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF65 and modulates alternative pre-mRNA splicing in vivo.
Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF65 and modulates alternative pre-mRNA splicing in vivo.
复制标题
DOI：
10.1261/rna.047258.114
复制
发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Suñé C
中科院分区：
文献类型：
--
作者：
Becerra S;Montes M;Hernández-Munain C;Suñé C
在哺乳动物中，剪接体在前体mRNA底物上组装过程中形成的第一个稳定复合物包括识别5′剪接位点的U1 snRNP，以及结合分支点序列、多聚嘧啶段和3′剪接位点的剪接因子SF 1和U2 AF。5′和3′剪接位点复合物被认为是通过蛋白质-蛋白质相互作用连接在一起的，蛋白质-蛋白质相互作用由确保初始剪接位点识别的保真度的因子介导。在这项研究中，我们确定和特点PRPF 40 B，一个假定的哺乳动物直系同源的U1 snRNP相关的酵母剪接因子Prp 40。PRPF 40 B在散斑中高度富集，具有类似于剪接因子的行为。我们证明PRPF 40 B直接与SF 1相互作用，并与U2 AF 65结合。因此，PRPF 40 B与这些剪接因子共定位在细胞核中。剪接试验与报告minigenes显示，PRPF 40 B调制选择性剪接位点选择。在Fas调控选择性剪接的情况下，弱的5′和3′剪接位点和外显子序列是PRPF 40 B功能所必需的。将我们的数据在一个功能的背景下，我们还表明，PRPF 40 B耗竭增加Fas/CD 95受体的数量和细胞凋亡，这表明PRPF 40 B的能力，改变选择性剪接的关键凋亡基因，以调节细胞存活。
The first stable complex formed during the assembly of spliceosomes onto pre-mRNA substrates in mammals includes U1 snRNP, which recognizes the 5′ splice site, and the splicing factors SF1 and U2AF, which bind the branch point sequence, polypyrimidine tract, and 3′ splice site. The 5′ and 3′ splice site complexes are thought to be joined together by protein–protein interactions mediated by factors that ensure the fidelity of the initial splice site recognition. In this study, we identified and characterized PRPF40B, a putative mammalian ortholog of the U1 snRNP-associated yeast splicing factor Prp40. PRPF40B is highly enriched in speckles with a behavior similar to splicing factors. We demonstrated that PRPF40B interacts directly with SF1 and associates with U2AF65. Accordingly, PRPF40B colocalizes with these splicing factors in the cell nucleus. Splicing assays with reporter minigenes revealed that PRPF40B modulates alternative splice site selection. In the case of Fas regulation of alternative splicing, weak 5′ and 3′ splice sites and exonic sequences are required for PRPF40B function. Placing our data in a functional context, we also show that PRPF40B depletion increased Fas/CD95 receptor number and cell apoptosis, which suggests the ability of PRPF40B to alter the alternative splicing of key apoptotic genes to regulate cell survival.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
LEGRAIN, P;SERAPHIN, B;ROSBASH, M
通讯作者：
ROSBASH, M
DOI：
10.1073/pnas.160266597
发表时间：
2000-08-01
影响因子：
11.1
作者：
Carty, SM;Goldstrohm, AC;Greenleaf, AL
通讯作者：
Greenleaf, AL
影响因子：
5.3
作者：
Lin, KT;Lu, RM;Tarn, WY
通讯作者：
Tarn, WY
Wolf Psort：蛋白质定位预测因子。
影响因子：
14.9
作者：
Horton, Paul;Park, Keun-Joon;Obayashi, Takeshi;Fujita, Naoya;Harada, Hajime;Adams-Collier, C J;Nakai, Kenta
通讯作者：
Nakai, Kenta