【がん研セミナー(3月11日)のお知らせ「Ending RNA messages in cancer cells」Dr. Takayuki Nojima (Associate Professor, Medical Institute of Bioregulation, Kyushu University)】
2024年02月06日
がん研セミナー(3月11日)のお知らせ
演題：Ending RNA messages in cancer cells
演者：Dr. Takayuki Nojima (Associate Professor, Medical Institute of Bioregulation, Kyushu University)
抄録：Transcription is terminated in appropriate region to produce functional messenger RNAs and also to prevent genome stresses (Ref 1, 2). However, the molecular mechanism of transcription termination remains largely unclear due to a technical limitation and a complexity caused by other co-transcriptional events. In this seminar, I will introduce a nascent RNA technology named mammalian native elongating transcript-sequencing (mNET-seq) method that reveals transcriptional dynamics with the phosphorylation states at single nucleotide resolution (Ref 3). In our mNET-seq analysis, RNA polymerase II (Pol II) machinery was specifically detected at termination region of protein coding genes with the CTD phosphorylation at threonine 4 position (T4P). On the other hand, the T4P CTD mark is distributed throughout long noncoding RNA (lncRNA) gene units, suggesting transcription termination signals are embedded in lncRNA genes to fine tune lncRNA expression (Ref 4). I substantially extended mNET-seq method to dissect intact nascent RNA associated with elongating Pol II machinery. This method was termed Polymerase Intact Nascent Transcript (POINT) technology (Ref 5). The POINT technology detects nascent transcript 5’ends at single nucleotide resolution (POINT-5) in illumina platform. Notably POINT-5 method precisely profiles co-transcriptional RNA cleavage sites that are critical for transcription termination. Finally, I will share some preliminary results of transcription termination regulation that is addicted in cancer.
References (* corresponding authors)
1.Nojima T* and Proudfoot NJ*.
Mechanism of lncRNA biogenesis as revealed by nascent transcriptomics. Nature Reviews Molecular Cell Biology, 23, 389-406, 2022
2.Nojima T*, Tellier M, Foxwell J, Rebeiro deA C, Tan-Wong SM, Dhir S, Dhir A, Murphy S* and Proudfoot NJ*.
Deregulated expression of lncRNA through loss of SPT6 induces R-loop, DNA replication stress and cellular senescence. Molecular Cell, 72:1-15, 2018
3.Nojima T, Gomes T, Fialho Grosso AR, Kimura H, Dye MJ, Dhir S, Carmo-Fonseca M* and Proudfoot NJ*. Mammalian NET-seq reveals genome-wide nascent transcription coupled to RNA processing. Cell, 23; 526-40, 2015
4.Schlackow M, Nojima T*, Gomes T, Dhir A, Carmo-Fonseca and Proudfoot NJ*.
Distinctive patterns of transcription and RNA processing for human lincRNA, Molecular Cell, 65:25-38, 2017
5.Sousa-Luis R, Dujardin G, Zukher I, Kimura H, Carmo-Fonseca M*, Proudfoot NJ*, and Nojima T*.
POINT Technology Illuminates the Processing of Polymerase-Associated Intact Nascent Transcripts. Molecular Cell, 81, 1935-1950, 2021
日時：２０２４年３月１１日（月） １７：００〜１８：００
場所：吉田記念講堂
演題：Ending RNA messages in cancer cells
演者：Dr. Takayuki Nojima (Associate Professor, Medical Institute of Bioregulation, Kyushu University)
抄録：Transcription is terminated in appropriate region to produce functional messenger RNAs and also to prevent genome stresses (Ref 1, 2). However, the molecular mechanism of transcription termination remains largely unclear due to a technical limitation and a complexity caused by other co-transcriptional events. In this seminar, I will introduce a nascent RNA technology named mammalian native elongating transcript-sequencing (mNET-seq) method that reveals transcriptional dynamics with the phosphorylation states at single nucleotide resolution (Ref 3). In our mNET-seq analysis, RNA polymerase II (Pol II) machinery was specifically detected at termination region of protein coding genes with the CTD phosphorylation at threonine 4 position (T4P). On the other hand, the T4P CTD mark is distributed throughout long noncoding RNA (lncRNA) gene units, suggesting transcription termination signals are embedded in lncRNA genes to fine tune lncRNA expression (Ref 4). I substantially extended mNET-seq method to dissect intact nascent RNA associated with elongating Pol II machinery. This method was termed Polymerase Intact Nascent Transcript (POINT) technology (Ref 5). The POINT technology detects nascent transcript 5’ends at single nucleotide resolution (POINT-5) in illumina platform. Notably POINT-5 method precisely profiles co-transcriptional RNA cleavage sites that are critical for transcription termination. Finally, I will share some preliminary results of transcription termination regulation that is addicted in cancer.
References (* corresponding authors)
1.Nojima T* and Proudfoot NJ*.
Mechanism of lncRNA biogenesis as revealed by nascent transcriptomics. Nature Reviews Molecular Cell Biology, 23, 389-406, 2022
2.Nojima T*, Tellier M, Foxwell J, Rebeiro deA C, Tan-Wong SM, Dhir S, Dhir A, Murphy S* and Proudfoot NJ*.
Deregulated expression of lncRNA through loss of SPT6 induces R-loop, DNA replication stress and cellular senescence. Molecular Cell, 72:1-15, 2018
3.Nojima T, Gomes T, Fialho Grosso AR, Kimura H, Dye MJ, Dhir S, Carmo-Fonseca M* and Proudfoot NJ*. Mammalian NET-seq reveals genome-wide nascent transcription coupled to RNA processing. Cell, 23; 526-40, 2015
4.Schlackow M, Nojima T*, Gomes T, Dhir A, Carmo-Fonseca and Proudfoot NJ*.
Distinctive patterns of transcription and RNA processing for human lincRNA, Molecular Cell, 65:25-38, 2017
5.Sousa-Luis R, Dujardin G, Zukher I, Kimura H, Carmo-Fonseca M*, Proudfoot NJ*, and Nojima T*.
POINT Technology Illuminates the Processing of Polymerase-Associated Intact Nascent Transcripts. Molecular Cell, 81, 1935-1950, 2021
日時：２０２４年３月１１日（月） １７：００〜１８：００
場所：吉田記念講堂
