两种 SEC 支架蛋白 AFF1 和 AFF4 在调节 RNA 聚合酶 II 转录伸长过程中的不同作用。

IF 5.3 2区 生物学 Q2 CELL BIOLOGY
Zhuanzhuan Che, Xiaoxu Liu, Qian Dai, Ke Fang, Chenghao Guo, Junjie Yue, Haitong Fang, Peng Xie, Zhuojuan Luo, Chengqi Lin
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引用次数: 0

摘要

含有正转录伸长因子 b 的超级伸长复合体(SEC)在调节转录伸长过程中发挥着关键作用。AFF1 和 AFF4 是 AF4/FMR2 家族的两个成员,它们是 SEC 的核心支架蛋白,与多种人类疾病相关。然而,它们在转录控制中的确切作用仍不清楚。在这里,我们研究了AFF1和AFF4在转录起始位点(TSSs)周围基因组分布模式的差异。AFF1 主要结合在 TSS 上游,而 AFF4 则富集在 TSS 下游。值得注意的是,破坏 AFF4 会导致与 AFF4 结合的活性基因亚群缓慢伸长并提前终止,而 AFF1 缺失则会导致同一基因亚群快速伸长和转录通读。此外,敲除 AFF1 会增加染色质中的 AFF4 水平,反之亦然。总之,这些研究结果表明,AFF1 和 AFF4 在调节 RNA 聚合酶 II 转录方面具有拮抗作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Distinct roles of two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA polymerase II transcription elongation.

The super elongation complex (SEC) containing positive transcription elongation factor b plays a critical role in regulating transcription elongation. AFF1 and AFF4, two members of the AF4/FMR2 family, act as central scaffold proteins of SEC and are associated with various human diseases. However, their precise roles in transcriptional control remain unclear. Here, we investigate differences in the genomic distribution patterns of AFF1 and AFF4 around transcription start sites (TSSs). AFF1 mainly binds upstream of the TSS, while AFF4 is enriched downstream of the TSS. Notably, disruption of AFF4 results in slow elongation and early termination in a subset of AFF4-bound active genes, whereas AFF1 deletion leads to fast elongation and transcriptional readthrough in the same subset of genes. Additionally, AFF1 knockdown increases AFF4 levels at chromatin, and vice versa. In summary, these findings demonstrate that AFF1 and AFF4 function antagonistically to regulate RNA polymerase II transcription.

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来源期刊
CiteScore
9.60
自引率
1.80%
发文量
1383
期刊介绍: The Journal of Molecular Cell Biology ( JMCB ) is a full open access, peer-reviewed online journal interested in inter-disciplinary studies at the cross-sections between molecular and cell biology as well as other disciplines of life sciences. The broad scope of JMCB reflects the merging of these life science disciplines such as stem cell research, signaling, genetics, epigenetics, genomics, development, immunology, cancer biology, molecular pathogenesis, neuroscience, and systems biology. The journal will publish primary research papers with findings of unusual significance and broad scientific interest. Review articles, letters and commentary on timely issues are also welcome. JMCB features an outstanding Editorial Board, which will serve as scientific advisors to the journal and provide strategic guidance for the development of the journal. By selecting only the best papers for publication, JMCB will provide a first rate publishing forum for scientists all over the world.
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