Article
Biotechnology & Applied Microbiology
Hong-Leong Cheah, Siti Aminah Ahmed, Thean-Hock Tang
Summary: This study establishes the transcription start site (TSS) landscape and small RNA (sRNA) profile of L. biflexa serovar Patoc through differential RNA-seq analysis, revealing 2726 TSSs and 603 sRNAs. These findings enhance our understanding of the regulatory networks in L. biflexa.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2023)
Review
Microbiology
Thi Tuong Vi Dang, Jessie Colin, Guilhem Janbon
Summary: Pathogenic fungi require delicate gene regulation mechanisms to adapt and survive in different environments. The usage of alternative transcription start sites (aTSS) in fungi plays a crucial role in fine-tuning gene expression, and disrupted control of aTSS can severely affect fungal growth and infectious capacity.
Article
Biochemical Research Methods
Dimitris Grigoriadis, Nikos Perdikopanis, Georgios K. Georgakilas, Artemis G. Hatzigeorgiou
Summary: This study presents DeepTSS, a novel computational method for processing CAGE samples, that combines genomic signal processing (GSP), DNA features, evolutionary conservation evidence and Deep Learning (DL) to provide accurate TSS predictions. Experimental results show that DeepTSS outperforms existing algorithms on all benchmarks.
BMC BIOINFORMATICS
(2022)
Article
Biochemical Research Methods
Christopher S. Juerges, Lars Doelken, Florian Erhard
Summary: The study introduces a comprehensive approach called iTiSS for accurately identifying TSS in any eukaryotic TSS profiling experiment, reducing false positives by jointly analyzing multiple complementary datasets.
Article
Multidisciplinary Sciences
Olga A. Nikolaitchik, Saiful Islam, Jonathan P. Kitzrow, Alice Duchon, Zetao Cheng, Yang Liu, Jonathan M. O. Rawson, Wei Shao, Maria Nikolaitchik, Mary F. Kearney, Frank Maldarelli, Karin Musier-Forsyth, Vinay K. Pathak, Wei-Shau Hu, Malcolm Martin
Summary: HIV-1 uses host RNA polymerase II (Pol II) to transcribe its genome and employs multiple transcription start sites (TSS). Selection of TSS is regulated by specific sequences near the TATA box and R. Mutants expressing specific RNA transcripts with different numbers of guanosines at the 5'-end exhibit replication defects compared to the wild-type. These findings highlight the importance of TSS selection for HIV-1 replication fitness and genome integrity during reverse transcription.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Virology
Siarhei Kharytonchyk, Cleo Burnett, Keshav Gc, Alice Telesnitsky
Summary: HIV-1 uses heterogeneous transcription start sites (TSSs) to generate two distinct RNA isoforms with different structures and functions. The shorter RNA is encapsidated while the longer RNA is excluded from virions. This mechanism is unique to HIV-1 and is determined by core promoter elements.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Eric J. Tomko, Olivia Luyties, Jenna K. Rimel, Chi-Lin Tsai, Jill O. Fuss, James Fishburn, Steven Hahn, Susan E. Tsutakawa, Dylan J. Taatjes, Eric A. Galburt
Summary: The general transcription factor TFIIH contains three ATP-dependent catalytic activities and functions in nucleotide excision repair and Pol II transcription initiation. While the functions are conserved between metazoans and yeast, yeast TFIIH drives transcription start-site scanning. Human and yeast core-TFIIH complexes lack processive translocation, with the yeast kinase module aiding in robust transcription start-site scanning.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Junliang Wang, Wei Chen, Wenjun Yue, Wenhong Hou, Feng Rao, Hanbing Zhong, Yuanming Qi, Ni Hong, Ting Ni, Wenfei Jin
Summary: This study developed a single-cell polyadenylation sequencing method to investigate the landscape of alternative polyadenylation (APA) at the single-cell level. The results showed that genes with multiple polyA sites in bulk data tend to use only one site in each single cell. Cell cycle genes were found to have high variation in polyA site usages. Furthermore, polyA site usage switch played an important role in cell cycle regulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Fang Liu, Yong-Fang Huang, Chang-Xian Wu, Long-Chuan Duan, Huan-Chun Chen, Zheng-Fei Liu
Summary: Brucella melitensis (B. melitensis) is an important bacterium that causes global zoonotic diseases. In this study, a novel genome-wide method called Capping-seq was proposed to improve gene annotation and explore potential functional sites in B. melitensis. The results revealed the preference of purine at the transcription start site (TSS) positions and the consensus sequences of the promoter elements. Analysis of the 5' ends of genes showed potential complex regulation in B. melitensis. Furthermore, the study identified leaderless genes involved in metabolic processes.
Editorial Material
Biochemistry & Molecular Biology
Alexandra Bergfort, Karla M. Neugebauer
Summary: Alfonso-Gonzalez et al. present an innovative combination of long-read sequencing approaches that reveal coupling between alternative transcription start sites and alternative polyadenylation site usage at a global level.
Article
Microbiology
Jonathan M. O. Rawson, Olga A. Nikolaitchik, Saurabh Shakya, Brandon F. Keele, Vinay K. Pathak, Wei-Shau Hu
Summary: HIV-1 selectively packages specific unspliced RNA species during genome packaging, and this mechanism is conserved in various primate lentiviruses.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemical Research Methods
Wenzhong Lin, Ping Qiu, Yixing Xu, Lihong Chen, Zujian Wu, Jie Zhang, Zhenguo Du
Summary: This study evaluates the use of in vitro cap-snatching of rice stripe virus (RSV) to study the transcription start sites (TSSs) of tomato yellow leaf curl virus (TYLCV). RNA extracted from TYLCV-infected plants was incubated with purified RSV ribonucleoproteins in a reaction mixture to in vitro cap-snatch RSV. Deep sequencing of the RSV mRNAs produced in the reaction allowed the identification of 28 TSSs in TYLCV. These results support the use of RSV's in vitro cap-snatching for studying geminiviral TSSs.
JOURNAL OF VIROLOGICAL METHODS
(2023)
Article
Biotechnology & Applied Microbiology
David W. McKellar, Madhav Mantri, Meleana M. Hinchman, John S. L. Parker, Praveen Sethupathy, Benjamin D. Cosgrove, Iwijn De Vlaminck
Summary: Spatial transcriptomics allows us to study the spatial context of gene expression. Current methods are limited to detecting a subset of RNA transcripts. By using enzymatic in situ polyadenylation of RNA, we are able to detect the full spectrum of RNAs, expanding the scope of research. Applying this approach, we studied skeletal muscle regeneration and viral-induced myocarditis, and made new discoveries.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hyun Je Kang, Hye-jin Eom, Hongtae Kim, Kyungjae Myung, Hyug Moo Kwon, Jang Hyun Choi
Summary: Transcription-replication conflicts can lead to DNA damage and genomic instability, with R-loops being a major source of these conflicts. The nuclear protein Thrap3 plays a critical role in regulating R-loop resolution, preventing their accumulation and DNA damage in cancer cells. This study sheds light on the mechanisms by which R-loops contribute to cancer development and the potential therapeutic implications of targeting Thrap3 in cancer treatment.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Immunology
Benedikt M. Markus, Benjamin S. Waldman, Hernan A. Lorenzi, Sebastian Lourido
Summary: The study reveals that Toxoplasma produces specific transcription start sites at different stages, leading to the generation of mRNA isoforms with distinct 5' termini. Additionally, there is pervasive divergent transcription and nucleosome occupancy around promoters, highlighting the chromatin contributions to transcription initiation. A precise TSS map can uncover motifs associated with transcription initiation and provide a critical resource for functional genomics in Toxoplasma.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Cell & Tissue Engineering
Ivo Ngundu Woogeng, Bogumil Kaczkowski, Imad Abugessaisa, Haiming Hu, Akihiro Tachibana, Yoshiki Sahara, Chung-Chau Hon, Akira Hasegawa, Noriko Sakai, Mitsuhiro Nishida, Hashimita Sanyal, Junki Sho, Keisuke Kajita, Takeya Kasukawa, Minoru Takasato, Piero Carninci, Akiko Maeda, Michiko Mandai, Erik Arner, Masayo Takahashi, Cody Kime
Summary: This study developed a faster reprogramming system to induce retinal pigment epithelium (RPE)-like cells from human fibroblasts. The induced RPE (iRPE) cells showed critical RPE benchmarks and significant integration in transplanted retinas. The comprehensive single-cell RNA sequencing analysis provided a detailed characterization of the best cells. The system may provide a robust method for retinal cell induction in basic research and affordable autologous human RPE tissue for regenerative cell therapy.
Article
Genetics & Heredity
Gijs W. E. Santen, Harry G. Leitch, Jan Cobben
Summary: The ACMG framework for variant interpretation is well-established and widely used, but guidelines for establishing gene-disease relationships have not been widely acknowledged or implemented. This manuscript emphasizes the importance of distinguishing between different types of gene-disease relationships and discusses the available approaches for establishing these relationships. It provides a checklist to evaluate gene-disease relationships for genes with limited information. Real-life examples are presented to highlight the importance of thorough consideration of gene-disease relationships. The authors hope that these considerations and checklist will assist clinicians and scientists in dealing with variants in genes without robustly ascertained gene-disease relationships.
Editorial Material
Biochemistry & Molecular Biology
Lynne Maquat, Rory Johnson, Saba Valadkhan, Piero Carninci
Correction
Multidisciplinary Sciences
Mathys Grapotte, Manu Saraswat, Chloe Bessiere, Christophe Menichelli, Jordan A. Ramilowski, Jessica Severin, Yoshihide Hayashizaki, Masayoshi Itoh, Michihira Tagami, Mitsuyoshi Murata, Miki Kojima-Ishiyama, Shohei Noma, Shuhei Noguchi, Takeya Kasukawa, Akira Hasegawa, Harukazu Suzuki, Hiromi Nishiyori-Sueki, Martin C. Frith, Clement Chatelain, Piero Carninci, Michiel J. L. de Hoon, Wyeth W. Wasserman, Laurent Brehelin, Charles-Henri Lecellier
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Niha Peshimam, Hani Farah, Richard Caswell, Sian Ellard, Wajanat Jan, Alistair D. Calder, Jan Cobben, Ujwal Kariholu, Harry G. Leitch
Summary: Sedaghatian type spondylometaphyseal dysplasia (SSMD) is a rare multi-system disorder characterized by skeletal, neurological, and cardiovascular abnormalities. This study reports a new family with two affected siblings and provides a detailed description of the phenotypic features. When shortened long bones are present along with significant brain abnormalities, a diagnosis of SSMD should be considered.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Damir Baranasic, Matthias Hortenhuber, Piotr J. Balwierz, Tobias Zehnder, Abdul Kadir Mukarram, Chirag Nepal, Csilla Varnai, Yavor Hadzhiev, Ada Jimenez-Gonzalez, Nan Li, Joseph Wragg, Fabio M. D'Orazio, Dorde Relic, Mikhail Pachkov, Noelia Diaz, Benjamin Hernandez-Rodriguez, Zelin Chen, Marcus Stoiber, Michael Dong, Irene Stevens, Samuel E. Ross, Anne Eagle, Ryan Martin, Oluwapelumi Obasaju, Sepand Rastegar, Alison C. McGarvey, Wolfgang Kopp, Emily Chambers, Dennis Wang, Hyejeong R. Kim, Rafael D. Acemel, Silvia Naranjo, Maciej Lapinski, Vanessa Chong, Sinnakaruppan Mathavan, Bernard Peers, Tatjana Sauka-Spengler, Martin Vingron, Piero Carninci, Uwe Ohler, Scott Allen Lacadie, Shawn M. Burgess, Cecilia Winata, Freek van Eeden, Juan M. Vaquerizas, Jose Luis Gomez-Skarmeta, Daria Onichtchouk, Ben James Brown, Ozren Bogdanovic, Erik van Nimwegen, Monte Westerfield, Fiona C. Wardle, Carsten O. Daub, Boris Lenhard, Ferenc Muller
Summary: Zebrafish, an important model organism for studying embryonic development and human diseases, lacks a systematic functional annotation program. The international DANIO-CODE consortium addressed this issue by creating a central repository to store and process zebrafish developmental functional genomic data. They improved existing annotations and identified over 140,000 cis-regulatory elements throughout development. They also compared regulatory elements and epigenomic landscapes between zebrafish and mouse, predicting functional relationships between them. This study extends the utility of zebrafish developmental genomics to mammals.
Article
Biochemical Research Methods
Jonathan Moody, Tsukasa Kouno, Jen-Chien Chang, Yoshinari Ando, Piero Carninci, Jay W. Shin, Chung-Chau Hon
Summary: The SCAFE software suite was developed to process sc-end5-seq data to de novo identify TSS clusters and generate tCRE-by-cell count matrix for downstream analyses.
Article
Multidisciplinary Sciences
Nicolas J. Pillon, Jonathon A. B. Smith, Petter S. Alm, Alexander V. Chibalin, Julia Alhusen, Erik Arner, Piero Carninci, Tomas Fritz, Julia Otten, Tommy Olsson, Sophie van Doorslaer de ten Ryen, Louise Deldicque, Kenneth Caidahl, Harriet Wallberg-Henriksson, Anna Krook, Juleen R. Zierath
Summary: This study reveals the role of exercise-responsive cytokines in skeletal muscle development and growth in individuals with normal glucose tolerance or type 2 diabetes. Acute exercise triggers an inflammatory response and increases immune cell infiltration. CXCL12 is associated with skeletal muscle remodeling and differentiation.
Article
Biochemistry & Molecular Biology
Caterina Gasperini, Kiril Tuntevski, Silvia Beatini, Roberta Pelizzoli, Amanda Lo Van, Damiano Mangoni, Rosa M. Cossu, Giovanni Pascarella, Paolo Bianchini, Pascal Bielefeld, Margherita Scarpato, Meritxell Pons-Espinal, Remo Sanges, Alberto Diaspro, Carlos P. Fitzsimons, Piero Carninci, Stefano Gustincich, Davide De Pietri Tonelli
Summary: Piwil2 is crucial for neurogenesis in the adult hippocampus, and its expression is related to the dynamic expression of piRNAs. Depletion of Mili and piRNAs affects aNPCs differentiation, induces senescence, and generates reactive glia in the adult hippocampus. Mili depletion results in the modulation of transcripts with sequences complementary or homologous to piRNAs, including repetitive elements and mRNAs encoding essential proteins for proper neurogenesis.
Article
Cell Biology
Kathleen R. Stewart-Morgan, Cristina E. Requena, Valentin Flury, Qian Du, Zoe Heckhausen, Petra Hajkova, Anja Groth
Summary: The researchers developed a mass spectrometry-based method called iDEMS to measure DNA modifications on metabolically labeled DNA. This method revealed a hemi-methylated landscape on nascent DNA and showed that methylation maintenance is slower than cell division in mouse embryonic stem cells. They also found that hydroxymethylation is asymmetric between sister strands, favoring the parental strand.
NATURE CELL BIOLOGY
(2023)
Article
Genetics & Heredity
Pauline Robbe, Kate E. Ridout, Dimitrios V. Vavoulis, Helene Dreau, Ben Kinnersley, Nicholas Denny, Daniel Chubb, Niamh Appleby, Anthony Cutts, Alex J. Cornish, Laura Lopez-Pascua, Ruth Clifford, Adam Burns, Basile Stamatopoulos, Maite Cabes, Reem Alsolami, Pavlos Antoniou, Melanie Oates, Doriane Cavalieri, Genomics England Research Consortium, Cll Pilot Consortium, Jane Gibson, Anika Prabhu, Ron Schwessinger, Daisy Jennings, Terena James, Uma Maheswari, Marti Duran-Ferrer, Piero Carninci, Samantha J. L. Knight, Robert Mansson, Jim Hughes, James Davies, Mark Ross, David Bentley, Jonathan C. Strefford, Stephen Devereux, Andrew R. Pettitt, Peter Hillmen, Mark J. Caulfield, Richard S. Houlston, Jose Martin-Subero, Anna Schuh
Summary: This study reports the whole-genome sequencing of 485 chronic lymphocytic leukemia patients and identifies a range of recurrent coding and noncoding genetic mutations. The study also provides a high-resolution map of structural variants, copy number changes, and global genome features, and demonstrates the relationship of these features with clinical outcomes.
Review
Cell Biology
John S. S. Mattick, Paulo P. P. Amaral, Piero Carninci, Susan Carpenter, Howard Y. Y. Chang, Ling-Ling Chen, Runsheng Chen, Caroline Dean, Marcel E. E. Dinger, Katherine A. A. Fitzgerald, Thomas R. R. Gingeras, Mitchell Guttman, Tetsuro Hirose, Maite Huarte, Rory Johnson, Chandrasekhar Kanduri, Philipp Kapranov, Jeanne B. B. Lawrence, Jeannie T. T. Lee, Joshua T. T. Mendell, Timothy R. R. Mercer, Kathryn J. J. Moore, Shinichi Nakagawa, John L. L. Rinn, David L. L. Spector, Igor Ulitsky, Yue Wan, Jeremy E. E. Wilusz, Mian Wu
Summary: Genes encoding lncRNAs are abundant in complex organisms and are transcribed by RNA polymerase I, II, and III, as well as processed introns. The classification and annotation of lncRNAs are challenging due to their various functions, isoforms, and interactions with other genes. These lncRNAs evolve rapidly, are cell type-specific, and regulate multiple cellular processes, including gene expression and translation control.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Cell Biology
Chi Wai Yip, Chung-Chau Hon, Kayoko Yasuzawa, Divya M. Sivaraman, Jordan A. Ramilowski, Youtaro Shibayama, Saumya Agrawal, Anika V. Prabhu, Callum Parr, Jessica Severin, Yan Jun Lan, Josee Dostie, Andreas Petri, Hiromi Nishiyori-Sueki, Michihira Tagami, Masayoshi Itoh, Fernando Lopez-Redondo, Tsukasa Kouno, Jen-Chien Chang, Joachim Luginbuhl, Masaki Kato, Mitsuyoshi Murata, Wing Hin Yip, Xufeng Shu, Imad Abugessaisa, Akira Hasegawa, Harukazu Suzuki, Sakari Kauppinen, Ken Yagi, Yasushi Okazaki, Takeya Kasukawa, Michiel de Hoon, Piero Carninci, Jay W. Shin
Summary: Within the FANTOM6 consortium, we conducted a large-scale knockdown of 200 lncRNAs in human iPSCs and explored their roles in self-renewal and pluripotency. We identified 36 lncRNAs that inhibit cell growth and 36 lncRNAs with molecular phenotypes, potentially affecting pluripotency.
Article
Engineering, Biomedical
Masaru Koido, Chung-Chau Hon, Satoshi Koyama, Hideya Kawaji, Yasuhiro Murakawa, Kazuyoshi Ishigaki, Kaoru Ito, Jun Sese, Nicholas F. Parrish, Yoichiro Kamatani, Piero Carninci, Chikashi Terao
Summary: A machine-learning model called MENTR has been developed to link genome sequence and non-coding RNA expression at the cell type level. This model can predict the effects of RNA transcription and identify genetic variants associated with complex traits.
NATURE BIOMEDICAL ENGINEERING
(2023)
Editorial Material
Oncology
Giovanni Pascarella, Martin Frith, Piero Carninci
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)