Ribosome profiling analysis reveals the roles of DDX41 in translational regulation
Ribosome profiling analysis reveals the roles of DDX41 in translational regulation
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DOI：
10.1007/s12185-023-03558-2
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发表时间：
2023-02
影响因子：
2.1
通讯作者：
Saruul Tungalag;S. Shinriki;Mayumi Hirayama;Akiko Nagamachi;A. Kanai;T. Inaba;H. Matsui
中科院分区：
文献类型：
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作者：
Saruul Tungalag;S. Shinriki;Mayumi Hirayama;Akiko Nagamachi;A. Kanai;T. Inaba;H. Matsui
在包括骨髓增生异常综合征和急性髓系白血病在内的髓系恶性肿瘤中已观察到DDX41突变，但这些疾病的潜在致病机制尚未完全阐明。DDX41蛋白是一种依赖于ATP的RNA解旋酶，在RNA代谢中发挥作用。我们先前的研究表明，DDX41通过促进新转录的前核糖体RNA的加工参与核糖体的生物发生。在这一发现的基础上，在这项研究中，我们利用核糖体图谱技术来研究DDX41在翻译中的参与。我们发现，DDX41基因敲除导致转录增加和减少。基因集浓缩分析和基因本体论分析都表明，在DDX41基因被敲除后，核糖体相关基因在翻译上得到了促进，部分原因是这些转录本的转录长度明显缩短，转录和翻译水平较高。此外，我们还发现，当DDX41水平较低时，具有5‘-末端寡嘧啶基序的转录本倾向于在翻译上上调。我们的数据表明，对于核糖体的生物发生，可能存在一种涉及DDX41的翻译调控反馈机制。
DDX41mutation has been observed in myeloid malignancies including myelodysplastic syndromes and acute myeloid leukemia, but the underlying causative mechanisms of these diseases have not been fully elucidated. The DDX41 protein is an ATP-dependent RNA helicase with roles in RNA metabolism. We previously showed that DDX41 is involved in ribosome biogenesis by promoting the processing of newly transcribed pre-ribosomal RNA. To build on this finding, in this study, we leveraged ribosome profiling technology to investigate the involvement of DDX41 in translation. We found that DDX41 knockdown resulted in both translationally increased and decreased transcripts. Both gene set enrichment analysis and gene ontology analysis indicated that ribosome-associated genes were translationally promoted after DDX41 knockdown, in part because these transcripts had significantly shorter transcript length and higher transcriptional and translational levels. In addition, we found that transcripts with 5’-terminal oligopyrimidine motifs tended to be translationally upregulated when the DDX41 level was low. Our data suggest that a translationally regulated feedback mechanism involving DDX41 may exist for ribosome biogenesis.