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Ribosome profiling analysis reveals the roles of DDX41 in translational regulation

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Abstract

DDX41 mutation 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.

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Data availability

Ribo-seq data is available in the DDBJ database (https://www.ddbj.nig.ac.jp/ddbj/index-e.html) under accession number DRA015477.

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Acknowledgements

We would like to express our deepest appreciation to Ms. Aya Higashi, Ms. Sachiko Sakata, Ms. Miyu Tanaka and Ms. Etsuko Sekimori for their technical assistance, and to Ms. Kazue Akita for clerical work. This work was supported by JSPS KAKENHI Grant Number 21K08419 and 18K08334, the Program of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science, the Japanese Society of Hematology Research Grant and the Foundation for Promotion of Cancer Research. We would like to express our gratitude for these financial supports.

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  1. Saruul Tungalag and Satoru Shinriki have contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Laboratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan

    Saruul Tungalag, Satoru Shinriki, Mayumi Hirayama & Hirotaka Matsui

  2. Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan

    Mayumi Hirayama

  3. Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Akiko Nagamachi & Toshiya Inaba

  4. Laboratory of Systems Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan

    Akinori Kanai

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  1. Saruul Tungalag
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Correspondence to Hirotaka Matsui.

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Tungalag, S., Shinriki, S., Hirayama, M. et al. Ribosome profiling analysis reveals the roles of DDX41 in translational regulation. Int J Hematol 117, 876–888 (2023). https://doi.org/10.1007/s12185-023-03558-2

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