2023/09/22 更新

写真a

イチハラ カズヤ
市原 知哉
ICHIHARA Kazuya
所属
大学院理学研究科 理学専攻 生命理学 助教
大学院担当
大学院理学研究科
学部担当
理学部 生命理学科
職名
助教

研究キーワード 2

  1. 翻訳

  2. バイオインフォマティクス

研究分野 2

  1. ライフサイエンス / 分子生物学

  2. ライフサイエンス / ゲノム生物学

経歴 4

  1. 名古屋大学大学院 理学研究科 理学専攻   助教

    2023年6月 - 現在

  2. 九州大学 生体防御医学研究所   分子医科学分野   学術研究員

    2023年4月 - 2023年5月

  3. 日本学術振興会 特別研究員 (PD)

    2022年4月 - 2023年3月

  4. 日本学術振興会   特別研究員 (DC1)

    2020年4月 - 2022年3月

学歴 2

  1. 九州大学   医学系学府医学専攻   博士課程

    2019年4月 - 2022年3月

  2. 九州大学   医学系学府医科学専攻   修士課程

    2017年4月 - 2019年3月

所属学協会 2

  1. 日本分子生物学会

  2. 日本RNA学会

受賞 1

  1. 第24回リトリート 最優秀ポスター賞

    2022年7月   九州大学 生体防御医学研究所  

 

論文 8

  1. The ASC‐1 complex promotes translation initiation by scanning ribosomes 査読有り

    Yuki Kito, Akinobu Matsumoto, Kazuya Ichihara, Chisa Shiraishi, Ronghao Tang, Atsushi Hatano, Masaki Matsumoto, Peixun Han, Shintaro Iwasaki, Keiichi I Nakayama

    The EMBO Journal     頁: e112869   2023年4月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:EMBO  

    DOI: 10.15252/embj.2022112869

  2. RPL3L-containing ribosomes determine translation elongation dynamics required for cardiac function. 査読有り 国際誌

    Chisa Shiraishi, Akinobu Matsumoto, Kazuya Ichihara, Taishi Yamamoto, Takeshi Yokoyama, Taisuke Mizoo, Atsushi Hatano, Masaki Matsumoto, Yoshikazu Tanaka, Eriko Matsuura-Suzuki, Shintaro Iwasaki, Shouji Matsushima, Hiroyuki Tsutsui, Keiichi I Nakayama

    Nature communications   14 巻 ( 1 ) 頁: 2131   2023年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Although several ribosomal protein paralogs are expressed in a tissue-specific manner, how these proteins affect translation and why they are required only in certain tissues have remained unclear. Here we show that RPL3L, a paralog of RPL3 specifically expressed in heart and skeletal muscle, influences translation elongation dynamics. Deficiency of RPL3L-containing ribosomes in RPL3L knockout male mice resulted in impaired cardiac contractility. Ribosome occupancy at mRNA codons was found to be altered in the RPL3L-deficient heart, and the changes were negatively correlated with those observed in myoblasts overexpressing RPL3L. RPL3L-containing ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-containing ribosomes altered translation elongation dynamics for the entire transcriptome, its effects were most pronounced for transcripts related to cardiac muscle contraction and dilated cardiomyopathy, with the abundance of the encoded proteins being correspondingly decreased. Our results provide further insight into the mechanisms and physiological relevance of tissue-specific translational regulation.

    DOI: 10.1038/s41467-023-37838-6

    PubMed

  3. Identification of unannotated coding sequences and their physiological functions 査読有り

    Kazuya Ichihara, Keiichi I Nakayama, Akinobu Matsumoto

    The Journal of Biochemistry     2022年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    Summary

    Most protein-coding sequences (CDSs) are predicted sequences based on criteria such as a size sufficient to encode a product of at least 100 amino acids and with translation starting at an AUG initiation codon. However, recent studies based on ribosome profiling and mass spectrometry have shown that several RNAs annotated as long noncoding RNAs (lncRNAs) are actually translated to generate polypeptides of fewer than 100 amino acids, and that many proteins are translated from near-cognate initiation codons such as CUG and GUG. Furthermore, studies of genetically engineered mouse models have revealed that such polypeptides and proteins contribute to diverse physiological processes. In this review, we describe the latest methods for the identification of unannotated CDSs and provide examples of their physiological functions.

    DOI: 10.1093/jb/mvac064

  4. Kastor and Polluks polypeptides encoded by a single gene locus cooperatively regulate VDAC and spermatogenesis 査読有り 国際誌

    Shintaro Mise, Akinobu Matsumoto, Keisuke Shimada, Toshiaki Hosaka, Masatomo Takahashi, Kazuya Ichihara, Hideyuki Shimizu, Chisa Shiraishi, Daisuke Saito, Mikita Suyama, Tomoharu Yasuda, Toru Ide, Yoshihiro Izumi, Takeshi Bamba, Tomomi Kimura-Someya, Mikako Shirouzu, Haruhiko Miyata, Masahito Ikawa, Keiichi I. Nakayama

    Nature Communications   13 巻 ( 1 ) 頁: 1071   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Although several long noncoding RNAs (lncRNAs) have recently been shown to encode small polypeptides, those in testis remain largely uncharacterized. Here we identify two sperm-specific polypeptides, Kastor and Polluks, encoded by a single mouse locus (Gm9999) previously annotated as encoding a lncRNA. Both Kastor and Polluks are inserted in the outer mitochondrial membrane and directly interact with voltage-dependent anion channel (VDAC), despite their different amino acid sequences. Male VDAC3-deficient mice are infertile as a result of reduced sperm motility due to an abnormal mitochondrial sheath in spermatozoa, and deficiency of both Kastor and Polluks also severely impaired male fertility in association with formation of a similarly abnormal mitochondrial sheath. Spermatozoa lacking either Kastor or Polluks partially recapitulate the phenotype of those lacking both. Cooperative function of Kastor and Polluks in regulation of VDAC3 may thus be essential for mitochondrial sheath formation in spermatozoa and for male fertility.

    DOI: 10.1038/s41467-022-28677-y

    PubMed

    その他リンク: https://www.nature.com/articles/s41467-022-28677-y

  5. Identification and characterization of novel proteins associated with CHD4 査読有り

    Chihiro Sakaguchi, Kazuya Ichihara, Akihiro Nita, Yuta Katayama, Keiichi I. Nakayama

    Genes to Cells   27 巻 ( 1 ) 頁: 61 - 71   2022年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1111/gtc.12909

    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/gtc.12909

  6. A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing 査読有り

    Akihiro Nita, Akinobu Matsumoto, Ronghao Tang, Chisa Shiraishi, Kazuya Ichihara, Daisuke Saito, Mikita Suyama, Tomoharu Yasuda, Gaku Tsuji, Masutaka Furue, Bumpei Katayama, Toshiyuki Ozawa, Teruasa Murata, Teruki Dainichi, Kenji Kabashima, Atsushi Hatano, Masaki Matsumoto, Keiichi I. Nakayama

    PLOS Genetics   17 巻 ( 8 ) 頁: e1009686   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science (PLoS)  

    Although long noncoding RNAs (lncRNAs) are transcripts that do not encode proteins by definition, some lncRNAs actually contain small open reading frames that are translated. TINCR (terminal differentiation–induced ncRNA) has been recognized as a lncRNA that contributes to keratinocyte differentiation. However, we here show that TINCR encodes a ubiquitin-like protein that is well conserved among species and whose expression was confirmed by the generation of mice harboring a FLAG epitope tag sequence in the endogenous open reading frame as well as by targeted proteomics. Forced expression of this protein promoted cell cycle progression in normal human epidermal keratinocytes, and mice lacking this protein manifested a delay in skin wound healing associated with attenuated cell cycle progression in keratinocytes. We termed this protein TINCR-encoded ubiquitin-like protein (TUBL), and our results reveal a role for TINCR in the regulation of keratinocyte proliferation and skin regeneration that is dependent on TUBL.

    DOI: 10.1371/journal.pgen.1009686

  7. Combinatorial analysis of translation dynamics reveals eIF2 dependence of translation initiation at near-cognate codons 査読有り 国際誌

    Kazuya Ichihara, Akinobu Matsumoto, Hiroshi Nishida, Yuki Kito, Hideyuki Shimizu, Yuichi Shichino, Shintaro Iwasaki, Koshi Imami, Yasushi Ishihama, Keiichi I Nakayama

    Nucleic Acids Research   49 巻 ( 13 ) 頁: 7298 - 7317   2021年7月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    <title>Abstract</title>
    Although ribosome-profiling and translation initiation sequencing (TI-seq) analyses have identified many noncanonical initiation codons, the precise detection of translation initiation sites (TISs) remains a challenge, mainly because of experimental artifacts of such analyses. Here, we describe a new method, TISCA (TIS detection by translation Complex Analysis), for the accurate identification of TISs. TISCA proved to be more reliable for TIS detection compared with existing tools, and it identified a substantial number of near-cognate codons in Kozak-like sequence contexts. Analysis of proteomics data revealed the presence of methionine at the NH2-terminus of most proteins derived from near-cognate initiation codons. Although eukaryotic initiation factor 2 (eIF2), eIF2A and eIF2D have previously been shown to contribute to translation initiation at near-cognate codons, we found that most noncanonical initiation events are most probably dependent on eIF2, consistent with the initial amino acid being methionine. Comprehensive identification of TISs by TISCA should facilitate characterization of the mechanism of noncanonical initiation.

    DOI: 10.1093/nar/gkab549

    PubMed

  8. Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis 査読有り 国際誌

    Yoshiharu Muto, Toshiro Moroishi, Kazuya Ichihara, Masaaki Nishiyama, Hideyuki Shimizu, Hidetoshi Eguchi, Kyoji Moriya, Kazuhiko Koike, Koshi Mimori, Masaki Mori, Yuta Katayama, Keiichi I. Nakayama

    Journal of Experimental Medicine   216 巻 ( 4 ) 頁: 950 - 965   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Rockefeller University Press  

    Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is a previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload elicited by FBXL5 ablation gave rise to oxidative stress, tissue damage, inflammation, and compensatory proliferation of hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting outcome of FBXL5 deficiency in the liver was also found to be effective in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis promoted by iron overload. In addition, dysregulation of FBXL5-mediated cellular iron homeostasis was found to be associated with poor prognosis in human HCC, suggesting that FBXL5 plays a key role in defense against hepatocarcinogenesis.

    DOI: 10.1084/jem.20180900

    PubMed

▼全件表示

書籍等出版物 1

  1. 未注釈ORFの同定とその生理機能

    市原知哉, 岩崎信太郎, 松本有樹修( 担当: 共著 ,  範囲: 40: 2003-2010)

    実験医学増刊  2022年7月 

MISC 2

  1. TranslatomeとProteomeの融合が切り開く未踏ORFの生物学

    松本有樹修, 市原知哉, 西田紘士, 今見考志, 石濱泰, 中山敬一  

    日本分子生物学会年会プログラム・要旨集(Web)44th 巻   2021年

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  2. 精密な翻訳開始点の同定により明らかとなったNon-AUG翻訳開始の分子機構と生物学的意義

    市原知哉, 松本有樹修, 西田紘士, 今見考志, 石濱泰, 中山敬一  

    日本分子生物学会年会プログラム・要旨集(Web)44th 巻   2021年

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講演・口頭発表等 3

  1. 精密な翻訳開始点の同定により明らかとなったNon-AUG翻訳開始の分子機構と生物学的意義

    市原 知哉, 松本 有樹修, 西田 紘士, 今見 考志, 石濱 泰, 中山 敬一

    第44回日本分子生物学会年会  2021年12月3日 

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    記述言語:日本語   会議種別:口頭発表(一般)  

  2. eIF2D recycles 40S ribosomal subunit during intrinsic ribosome destabilization (IRD)

    Kazuya Ichihara, Yuhei Chadani, Atsushi Hatano, Masaki Matsumoto, Hideki Taguchi, Keiichi I Nakayama, Akinobu Matsumoto

    第24回日本RNA学会年会  2023年7月6日 

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    記述言語:日本語   会議種別:口頭発表(一般)  

  3. Combinatorial analysis of translation dynamics reveals eIF2 dependence of translation initiation at near-cognate codons

    Kazuya Ichihara, Akinobu Matsumoto, Hiroshi Nishida, Yuki Kito, Hideyuki Shimizu, Yuichi Shichino, Shintaro Iwasaki, Koshi Imami, Yasushi Ishihama, Keiichi I Nakayama

    2021年度日本バイオインフォマティクス学会年会・第10回生命医薬情報学連合大会  2021年9月28日 

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    記述言語:日本語   会議種別:口頭発表(一般)  

科研費 1

  1. ユビキチン修飾による鉄代謝制御系の最上流因子の探索

    研究課題/研究課題番号:20J20906  2020年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    市原 知哉

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    担当区分:研究代表者 

    配分額:2500000円 ( 直接経費:2500000円 )

 

担当経験のある科目 (本学以外) 1

  1. バイオインフォマティクス

    九州大学 生体防御医学研究所)