A protein-RNA interaction atlas of the ribosome biogenesis factor AATF

A protein-RNA interaction atlas of the ribosome biogenesis factor AATF
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核糖体生物合成因子 AATF 的蛋白质-RNA 相互作用图谱

DOI:
10.1038/s41598-019-47552-3
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发表时间:
2019
期刊:
影响因子:
4.6
通讯作者:
Dieterich
Dieterich
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kaiser;Ignarski;Van Nostrand;Cukoski;Heinen;Schaechter;Seufert;Frommolt;Keller;Schermer;Benzing;Hopker;Dieterich

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AATF 是 p53 激活后细胞结果的中心调节因子,这一发现主要归因于其作为转录因子的功能。最近的数据表明,AATF 对于核糖体生物发生至关重要,并在 rRNA 成熟中发挥作用。 AATF 通过与 rRNA 直接相互作用来发挥这一作用,并在多个 RNA 相互作用组捕获实验中得到鉴定。在这里,我们使用 CLIP 测序对 AATF 结合的 RNA 进行了首次全面分析。有趣的是,这种方法显示了 45S 前核糖体 RNA 前体分子的主要结合。此外,AATF 与编码核糖体生物合成因子的 mRNA 以及 snoRNA 结合。这些发现得到了对 AATF 蛋白质相互作用组的深入分析的补充,其中包含大量已知在 rRNA 成熟中发挥作用的蛋白质,重点是已知产生小核糖体亚基 (SSU) 所需的蛋白质-RNA 复合物。与这一发现一致,45S rRNA 前体中 AATF 的结合位点靠近 SSU 切割位点。因此,我们对 AATF 的蛋白质-RNA 相互作用组的多层分析表明,该蛋白质是参与核糖体生物发生的蛋白质和 RNA 相互作用的重要枢纽。
AATF is a central regulator of the cellular outcome upon p53 activation, a finding that has primarily been attributed to its function as a transcription factor. Recent data showed that AATF is essential for ribosome biogenesis and plays a role in rRNA maturation. AATF has been implicated to fulfil this role through direct interaction with rRNA and was identified in several RNA-interactome capture experiments. Here, we provide a first comprehensive analysis of the RNA bound by AATF using CLIP-sequencing. Interestingly, this approach shows predominant binding of the 45S pre-ribosomal RNA precursor molecules. Furthermore, AATF binds to mRNAs encoding for ribosome biogenesis factors as well as snoRNAs. These findings are complemented by an in-depth analysis of the protein interactome of AATF containing a large set of proteins known to play a role in rRNA maturation with an emphasis on the protein-RNA-complexes known to be required for the generation of the small ribosomal subunit (SSU). In line with this finding, the binding sites of AATF within the 45S rRNA precursor localize in close proximity to the SSU cleavage sites. Consequently, our multilayer analysis of the protein-RNA interactome of AATF reveals this protein to be an important hub for protein and RNA interactions involved in ribosome biogenesis.
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