A functional interaction between the survival motor neuron complex and RNA polymerase II.
A functional interaction between the survival motor neuron complex and RNA polymerase II.
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DOI：
10.1083/jcb.152.1.75
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发表时间：
2001-01-08
期刊：
影响因子：
--
通讯作者：
Dreyfuss G
中科院分区：
文献类型：
--
作者：
Pellizzoni L;Charroux B;Rappsilber J;Mann M;Dreyfuss G
运动神经元存活蛋白（SMN）是脊髓性肌萎缩症（SMA）基因的蛋白产物，在小核核糖核蛋白（snRNP）和剪接体的组装和再生中起作用。通过纳米电喷雾质谱，我们确定RNA解旋酶A（RHA）作为SMN复合物相关蛋白。RHA是DEAH盒RNA解旋酶，其结合RNA聚合酶II（pol II）并且据报道在转录中起作用。SMN在体外与RHA相互作用，并且这种相互作用在SMA患者中发现的突变SMN中受损。免疫共沉淀表明，SMN复合物与pol II，snRNP和RHA在体内。体外实验表明，RHA介导SMN与pol II的COOH末端结构域的关联。此外，用SMN的显性失活突变体SMNΔN27转染细胞，导致pol II、snRNP和RHA在含有已知的gems和卷曲体标记物的核结构中积累，并抑制RNA pol I和pol II在体内的转录。这些发现表明SMN复合物与pol II的功能和物理关联，并表明SMN复合物在pol II转录/加工机制的组装中的作用。
The survival motor neuron (SMN) protein, the protein product of the spinal muscular atrophy (SMA) disease gene, plays a role in the assembly and regeneration of small nuclear ribonucleoproteins (snRNPs) and spliceosomes. By nanoelectrospray mass spectrometry, we identified RNA helicase A (RHA) as an SMN complex–associated protein. RHA is a DEAH box RNA helicase which binds RNA polymerase II (pol II) and reportedly functions in transcription. SMN interacts with RHA in vitro, and this interaction is impaired in mutant SMNs found in SMA patients. Coimmunoprecipitation demonstrated that the SMN complex is associated with pol II, snRNPs, and RHA in vivo. In vitro experiments suggest that RHA mediates the association of SMN with the COOH-terminal domain of pol II. Moreover, transfection of cells with a dominant negative mutant of SMN, SMNΔN27, causes accumulation of pol II, snRNPs, and RHA in nuclear structures that contain the known markers of gems and coiled bodies, and inhibits RNA pol I and pol II transcription in vivo. These findings indicate a functional as well as physical association of the SMN complex with pol II and suggest a role for the SMN complex in the assembly of the pol II transcription/processing machinery.
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影响因子：
4.8
作者：
Friesen, MJ;Dreyfuss, G
通讯作者：
Dreyfuss, G
DOI：
10.1083/jcb.129.2.287
发表时间：
1995-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bregman DB;Du L;van der Zee S;Warren SL
通讯作者：
Warren SL
影响因子：
3.5
作者：
Hannus, S;Bühler, D;Fischer, U
通讯作者：
Fischer, U
影响因子：
3.5
作者：
Coovert, DD;Le, TT;Burghes, AHM
通讯作者：
Burghes, AHM
影响因子：
10.5
作者：
Cho, H;Kim, TK;Reinberg, D
通讯作者：
Reinberg, D