A protein complex regulates RNA processing of intronic heterochromatin-containing genes in Arabidopsis
A protein complex regulates RNA processing of intronic heterochromatin-containing genes in Arabidopsis
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DOI：
10.1073/pnas.1710683114
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发表时间：
2017-08-29
影响因子：
11.1
通讯作者：
Zhu, Jian-Kang
中科院分区：
文献类型：
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作者：
Duan, Cheng-Guo;Wang, Xingang;Zhu, Jian-Kang
在一些真核生物中，基因内含子中的异染色质（HC）可以调节RNA加工，包括聚腺苷酸化，但这种调节的机制知之甚少。通过促进远端聚腺苷酸化，含溴邻近同源（BAH）结构域和RNA识别基序的蛋白ASI 1和H3 K9 me 2结合蛋白EDM 2是拟南芥中内含子含HC基因的功能性全长转录本表达所必需的。在这里，我们报告说，ASI 1和EDM 2形成一个蛋白质复合物在体内通过一个桥梁蛋白，ASI 1-免疫沉淀蛋白1（AIPP 1），这是另一个RNA识别基序包含蛋白。该复合物还可以含有Pol II CTD磷酸酶CPL 2、含有植物同源结构域的蛋白AIPP 2和另一种BAH结构域蛋白AIPP 3。与ASI 1和EDM 2功能障碍的情况一样，AIPP 1功能障碍阻碍了在测试的内含子含HC基因（如组蛋白脱甲基酶基因IBM 1）处使用远端聚腺苷酸化位点，导致功能性全长转录物的缺乏。AIPP 1的突变导致35 S-SUC 2转基因沉默和基因体区域的全基因组CHG超甲基化，这与突变体中全长功能性IBM 1转录物的缺乏一致。有趣的是，与asi 1、edm 2和aipp 1突变相比，CPL 2、AIPP 2和AIPP 3突变对内含子含HC基因和其他基因的表达产生相反的影响，这表明CPL 2、AIPP 2和AIPP 3可能形成不同的亚复合物。这些结果推进了我们对高等真核生物异染色质表观遗传修饰和RNA加工之间相互作用的理解。
In several eukaryotic organisms, heterochromatin (HC) in the introns of genes can regulate RNA processing, including polyadenylation, but the mechanism underlying this regulation is poorly understood. By promoting distal polyadenylation, the bromo-adjacent homology (BAH) domain-containing and RNA recognition motif-containing protein ASI1 and the H3K9me2-binding protein EDM2 are required for the expression of functional full-length transcripts of intronic HC-containing genes in Arabidopsis. Here we report that ASI1 and EDM2 form a protein complex in vivo via a bridge protein, ASI1-Immunoprecipitated Protein 1 (AIPP1), which is another RNA recognition motif-containing protein. The complex also may contain the Pol II CTD phosphatase CPL2, the plant homeodomain-containing protein AIPP2, and another BAH domain protein, AIPP3. As is the case with dysfunction of ASI1 and EDM2, dysfunction of AIPP1 impedes the use of distal polyadenylation sites at tested intronic HC-containing genes, such as the histone demethylase gene IBM1, resulting in a lack of functional full-length transcripts. A mutation in AIPP1 causes silencing of the 35S-SUC2 transgene and genome-wide CHG hypermethylation at gene body regions, consistent with the lack of full-length functional IBM1 transcripts in the mutant. Interestingly, compared with asi1, edm2, and aipp1 mutations, mutations in CPL2, AIPP2, and AIPP3 cause the opposite effects on the expression of intronic HC-containing genes and other genes, suggesting that CPL2, AIPP2, and AIPP3 may form a distinct subcomplex. These results advance our understanding of the interplay between heterochromatic epigenetic modifications and RNA processing in higher eukaryotes.