The α-like RNA polymerase II core subunit 3 (RPB3) is involved in tissue-specific transcription and muscle differentiation via interaction with the myogenic factor myogenin
The α-like RNA polymerase II core subunit 3 (RPB3) is involved in tissue-specific transcription and muscle differentiation via interaction with the myogenic factor myogenin
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DOI：
10.1096/fj.02-0123fje
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发表时间：
2002-08-01
期刊：
影响因子：
4.8
通讯作者：
Passananti, C
中科院分区：
文献类型：
--
作者：
Corbi, N;Di Padova, M;Passananti, C
RNA聚合酶II核心亚基3（RPB 3）是RNA聚合酶II（pol II）的α样核心亚基。用阿霉素（dox）治疗后，它会选择性下调。由于暴露于dox时骨骼肌细胞不能分化，我们假设RPB 3参与肌肉分化。为此，我们已经分离出人肌肉RPB 3相互作用蛋白，通过使用酵母双杂交筛选。令人感兴趣的是，RPB 3和肌生成转录因子肌生成素之间的相互作用被鉴定。这种相互作用涉及RPB 3蛋白的一个特定区域，该区域与原核α亚基不同源。虽然RPB 3接触肌细胞生成素的碱性螺旋-环-螺旋（HLH）区域，但它不结合其他HLH肌细胞生成因子，如MyoD、Myf 5和MRF 4。免疫共沉淀实验表明，肌细胞生成素接触的聚合酶II复合物和RPB 3亚基是负责这种相互作用。我们发现，RPB 3的表达在肌肉分化过程中受到调节。RPB 3的外源性表达轻微地促进肌细胞生成素反式激活活性和肌肉分化，而RPB 3的与肌细胞生成素接触的区域，当用作显性负性分子（Sud）时，抵消这些作用。这些结果首次表明RPB 3 pol II亚基参与组织特异性转录的调节。
RNA polymerase II core subunit 3 (RPB3) is an alpha-like core subunit of RNA polymerase II (pol II). It is selectively down-regulated upon treatment with doxorubicin (dox). Due to the failure of skeletal muscle cells to differentiate when exposed to dox, we hypothesized that RPB3 is involved in muscle differentiation. To this end, we have isolated human muscle RPB3-interacting proteins by using yeast two-hybrid screening. It is of interest that an interaction between RPB3 and the myogenic transcription factor myogenin was identified. This interaction involves a specific region of RPB3 protein that is not homologous to the prokaryotic alpha subunit. Although RPB3 contacts the basic helix-loop-helix (HLH) region of myogenin, it does not bind other HLH myogenic factors such as MyoD, Myf5, and MRF4. Coimmunoprecipitation experiments indicate that myogenin contacts the pol II complex and that the RPB3 subunit is responsible for this interaction. We show that RPB3 expression is regulated during muscle differentiation. Exogenous expression of RPB3 slightly promotes myogenin transactivation activity and muscle differentiation, whereas the region of RPB3 that contacts myogenin, when used as a dominant negative molecule (Sud), counteracts these effects. These results indicate for the first time that the RPB3 pol II subunit is involved in the regulation of tissue-specific transcription.