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Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping 期刊论文
NATURE, 2020, 583 (7817) : 638-+
作者:  Lin, Yiheng;  Leibrandt, David R.;  Leibfriedz, Dietrich;  Chou, Chin-wen
收藏  |  浏览/下载:26/0  |  提交时间:2020/07/03

A method termed ac(4)C-seq is introduced for the transcriptome-wide mapping of the RNA modificationN(4)-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.


N-4-acetylcytidine (ac(4)C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA(1-3). However, the distribution, dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac(4)C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac(4)C at single-nucleotide resolution. In human and yeast mRNAs, ac(4)C sites are not detected but can be induced-at a conserved sequence motif-via the ectopic overexpression of eukaryotic acetyltransferase complexes. By contrast, cross-evolutionary profiling revealed unprecedented levels of ac(4)C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. (AcC)-C-4 is markedly induced in response to increases in temperature, and acetyltransferase-deficient archaeal strains exhibit temperature-dependent growth defects. Visualization of wild-type and acetyltransferase-deficient archaeal ribosomes by cryo-electron microscopy provided structural insights into the temperature-dependent distribution of ac(4)C and its potential thermoadaptive role. Our studies quantitatively define the ac(4)C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease(4-6).


  
Mass-spectrometry-based draft of the Arabidopsis proteome 期刊论文
NATURE, 2020
作者:  Vasanthakumar, Ajithkumar;  Chisanga, David;  Blume, Jonas;  Gloury, Renee;  Britt, Kara;  Henstridge, Darren C.;  Zhan, Yifan;  Torres, Santiago Valle;  Liene, Sebastian;  Collins, Nicholas;  Cao, Enyuan;  Sidwell, Tom;  Li, Chaoran;  Spallanzani, Raul German;  Liao, Yang;  Beavis, Paul A.;  Gebhardt, Thomas;  Trevaskis, Natalie;  Nutt, Stephen L.;  Zajac, Jeffrey D.;  Davey, Rachel A.;  Febbraio, Mark A.;  Mathis, Diane;  Shi, Wei;  Kallies, Axel
收藏  |  浏览/下载:37/0  |  提交时间:2020/07/03

Plants are essential for life and are extremely diverse organisms with unique molecular capabilities(1). Here we present a quantitative atlas of the transcriptomes, proteomes and phosphoproteomes of 30 tissues of the model plant Arabidopsis thaliana. Our analysis provides initial answers to how many genes exist as proteins (more than 18,000), where they are expressed, in which approximate quantities (a dynamic range of more than six orders of magnitude) and to what extent they are phosphorylated (over 43,000 sites). We present examples of how the data may be used, such as to discover proteins that are translated from short open-reading frames, to uncover sequence motifs that are involved in the regulation of protein production, and to identify tissue-specific protein complexes or phosphorylation-mediated signalling events. Interactive access to this resource for the plant community is provided by the ProteomicsDB and ATHENA databases, which include powerful bioinformatics tools to explore and characterize Arabidopsis proteins, their modifications and interactions.


A quantitative atlas of the transcriptomes, proteomes and phosphoproteomes of 30 tissues of the model plant Arabidopsis thaliana provides a valuable resource for plant research.


  
Peripheral T cell expansion predicts tumour infiltration and clinical response 期刊论文
NATURE, 2020, 579 (7798) : 274-+
作者:  Yasuda, Sayaka;  Tsuchiya, Hikaru;  Kaiho, Ai;  Guo, Qiang;  Ikeuchi, Ken;  Endo, Akinori;  Arai, Naoko;  Ohtake, Fumiaki;  Murata, Shigeo;  Inada, Toshifumi;  Baumeister, Wolfgang;  Fernandez-Busnadiego, Ruben;  Tanaka, Keiji;  Saeki, Yasushi
收藏  |  浏览/下载:18/0  |  提交时间:2020/07/03

Despite the resounding clinical success in cancer treatment of antibodies that block the interaction of PD1 with its ligand PDL1(1), the mechanisms involved remain unknown. A major limitation to understanding the origin and fate of T cells in tumour immunity is the lack of quantitative information on the distribution of individual clonotypes of T cells in patients with cancer. Here, by performing deep single-cell sequencing of RNA and T cell receptors in patients with different types of cancer, we survey the profiles of various populations of T cells and T cell receptors in tumours, normal adjacent tissue, and peripheral blood. We find clear evidence of clonotypic expansion of effector-like T cells not only within the tumour but also in normal adjacent tissue. Patients with gene signatures of such clonotypic expansion respond best to anti-PDL1 therapy. Notably, expanded clonotypes found in the tumour and normal adjacent tissue can also typically be detected in peripheral blood, which suggests a convenient approach to patient identification. Analyses of our data together with several external datasets suggest that intratumoural T cells, especially in responsive patients, are replenished with fresh, non-exhausted replacement cells from sites outside the tumour, suggesting continued activity of the cancer immunity cycle in these patients, the acceleration of which may be associated with clinical response.