『超高解像度新生RNA 解析法の開発とゲノム転写制御の研究』

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1101/2024.01.31.578294

その他リンク： https://www.biorxiv.org/content/10.1101/2024.01.31.578294v1

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular Cell  

Many spliceosomal introns are excised from nascent transcripts emerging from RNA polymerase II (RNA Pol II). The extent of cell-type-specific regulation and possible functions of such co-transcriptional events remain poorly understood. We examined the role of the RNA-binding protein PTBP1 in this process using an acute depletion approach followed by the analysis of chromatin- and RNA Pol II-associated transcripts. We show that PTBP1 activates the co-transcriptional excision of hundreds of introns, a surprising effect given that this protein is known to promote intron retention. Importantly, some co-transcriptionally activated introns fail to complete their splicing without PTBP1. In a striking example, retention of a PTBP1-dependent intron triggers nonsense-mediated decay of transcripts encoding DNA methyltransferase DNMT3B. We provide evidence that this regulation facilitates the natural decline in DNMT3B levels in developing neurons and protects differentiation-specific genes from ectopic methylation. Thus, PTBP1-activated co-transcriptional splicing is a widespread phenomenon mediating epigenetic control of cellular identity.

DOI： 10.1016/j.molcel.2022.12.014

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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：EMBO Reports  

CDK9 is a kinase critical for the productive transcription of protein-coding genes by RNA polymerase II (pol II). As part of P-TEFb, CDK9 phosphorylates the carboxyl-terminal domain (CTD) of pol II and elongation factors, which allows pol II to elongate past the early elongation checkpoint (EEC) encountered soon after initiation. We show that, in addition to halting pol II at the EEC, loss of CDK9 activity causes premature termination of transcription across the last exon, loss of polyadenylation factors from chromatin, and loss of polyadenylation of nascent transcripts. Inhibition of the phosphatase PP2A abrogates the premature termination and loss of polyadenylation caused by CDK9 inhibition, indicating that this kinase/phosphatase pair regulates transcription elongation and RNA processing at the end of protein-coding genes. We also confirm the splicing factor SF3B1 as a target of CDK9 and show that SF3B1 in complex with polyadenylation factors is lost from chromatin after CDK9 inhibition. These results emphasize the important roles that CDK9 plays in coupling transcription elongation and termination to RNA maturation downstream of the EEC.

DOI： 10.15252/embr.202154520

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Reviews Molecular Cell Biology  

Mammalian genomes express two principal gene categories through RNA polymerase II-mediated transcription: protein-coding transcription units and non-coding RNA transcription units. Non-coding RNAs are further divided into relatively abundant structural RNAs, such as small nuclear RNAs, and into a myriad of long non-coding RNAs (lncRNAs) of often low abundance and low stability. Although at least some lncRNA synthesis may reflect transcriptional ‘noise’, recent studies define unique functions for either specific lncRNAs or for the process of lncRNA synthesis. Notably, the transcription, processing and metabolism of lncRNAs are regulated differently from protein-coding genes. In this Review, we provide insight into the regulation of lncRNA transcription and processing gleaned from the application of recently devised nascent transcriptomics technology. We first compare and contrast different methodologies for studying nascent transcription. We then discuss the molecular mechanisms regulating lncRNA transcription, especially transcription initiation and termination, which emphasize fundamental differences in their expression as compared with protein-coding genes. When perturbed, lncRNA misregulation leads to genomic stress such as transcription–replication conflict and R-loop-mediated DNA damage. We discuss many unresolved but important questions about the synthesis and potential functions of lncRNAs.

DOI： 10.1038/s41580-021-00447-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1101/2020.11.09.374108

その他リンク： https://www.sciencedirect.com/science/article/pii/S1097276521001441?via%3Dihub

開催年月日： 2023年10月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

国名：日本国  

開催年月日： 2022年1月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

その他リンク： http://hshis30.umin.ne.jp/

開催年月日： 2021年11月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

その他リンク： https://www.keyforum2021.org/

開催年月日： 2021年10月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2023年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：国立遺伝学研究所   国名：日本国  

記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

DOI： https://doi.org/10.1038/s41580-021-00447-6

その他リンク： https://www.nature.com/articles/s41580-021-00447-6

記述言語：英語   出版者・発行元：Nature Reviews Molecular Cell Biology  

In the version of this article initially published, the technique fastGRO was presented in Fig. 2 and the main text as a chromatin- based run- on technique when in fact it is a nuclear run- on technique. Accordingly, in Fig. 2, right- hand “Techniques” section, the third balloon has been edited to include “fastGRO” and the seventh balloon edited to remove “fastGRO,” and the eighth sentence of the Fig. 2 legend has been amended to include fastGRO, as follows: “Nucleus: transcription run- on (TRO) analyses are performed in biochemically isolated nuclei using 5-bromouridine 5′-triphosphate (BrUTP) in GRO-seq37, 4- thiouridine (4sU) in fastGRO40 or biotin- labelled NTPs (biotin- NTP) in PRO- seq38.” Further, the penultimate sentence of the “In vitro RNA labelling” section has been amended to read “Finally, a variation on genomic TRO called fastGRO also employs 4- thiouridine (4sU) in the NRO reaction” (from the original “Finally, a variation on genomic TRO called fastGRO also employs the use of chromatin fractions as starting material but the nascent transcript is tagged with 4- thiouridine (4sU)….”). The changes are reflected in the HTML and PDF versions of the article.

DOI： 10.1038/s41580-022-00551-1

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種別：大会・シンポジウム等 

参加者数：50

種別：大会・シンポジウム等 

参加者数：50