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.
Editorial Material
Multidisciplinary Sciences
Elie Dolgin
Summary: Immunotherapy is showing promise in treating solid tumors, but researchers are calling for more dedicated research specifically focused on young people.
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)
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
Multidisciplinary Sciences
Vanessa Zaiatz-Bittencourt, Fiona Jones, Miriam Tosetto, Caitriona Scaife, Gerard Cagney, Evan Jones, Glen A. Doherty, Elizabeth J. Ryan
Summary: The gut microbiota plays a crucial role in regulating chronic inflammation and its involvement in the development of autoimmune diseases and cancer. Microbial short-chain fatty acids, such as butyrate, have immunomodulatory effects and are believed to mediate the host-microbiome interaction. This study demonstrates that butyrate has a strong anti-inflammatory effect on NK cells and restricts their function through downregulation of mTORC1 activity, c-Myc mRNA expression, and metabolism.
SCIENTIFIC REPORTS
(2023)
Editorial Material
Biology
Igor Martianov, Irwin Davidson
Summary: Experimental results show that RNA polymerase II transcription can still occur efficiently in mouse embryonic stem cells even in the absence of TBP and TBP-like proteins, suggesting that this initiation factor may not be as essential as previously thought.
Article
Multidisciplinary Sciences
Ka Lung Cheung, Anbalagan Jaganathan, Yuan Hu, Feihong Xu, Alannah Lejeune, Rajal Sharma, Cristina I. Caescu, Jamel Meslamani, Adam Vincek, Fan Zhang, Kyung Lee, Nilesh Zaware, Amina Abdul Qayum, Chunyan Ren, Mark H. Kaplan, John Cijiang He, Huabao Xiong, Ming-Ming Zhou
Summary: This study uncovers a previously unrecognized mechanism of self-directed cell type-specific regulation of the master transcription factor Stat3 through its own transcriptional target Hipk2 in Th17 cell differentiation. These findings provide insights into the regulation of Th17 cell immune functions and suggest a therapeutic strategy for developing targeted therapies for Th17-associated inflammatory disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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)
Review
Biochemical Research Methods
Debomita Chakraborty, Raghunathan Rengaswamy, Karthik Raman
Summary: This paper systematically organizes key works in the field of genetic circuit design using the framework of generalized morphological analysis. It maps literature based on design methodologies, modeling techniques, circuit functionalities, design characteristics, and strategies for robust design. The paper concludes with an outlook on future research areas based on the assessment of research gaps.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Computer Science, Artificial Intelligence
Jose A. Barbero-Aparicio, Alicia Olivares-Gil, Jose F. Diez-Pastor, Cesar Garcia-Osorio
Summary: Recognizing transcription start sites is crucial for gene identification. This article compares the performance of support vector machines (SVMs) and deep learning methods, specifically long short-term memory neural networks (LSTMs), in predicting transcription start sites. The results show that deep learning methods are better suited for this task, especially when working with sequence data. Additionally, a method for generating transcription start site datasets and the importance of balanced data are discussed.
PEERJ COMPUTER SCIENCE
(2023)
Article
Plant Sciences
Andrew Murray, John Pablo Mendieta, Chris Vollmers, Robert J. Schmitz
Summary: The accurate identification and quantification of transcriptional start sites (TSSs) is crucial for understanding transcription control. In this study, the researchers developed Smar2C2, a new method that allows for the easy and efficient identification of TSSs and transcription termination sites. Using this method, they were able to identify TSSs in multiple plant species and discover evolutionarily conserved features as well as sequence variations in known promoter motifs that may have significant implications for our understanding and control of transcription initiation.
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)
Article
Multidisciplinary Sciences
Aleksandr Ianevski, Anil K. Giri, Tero Aittokallio
Summary: We developed a computational platform, ScType, for automated and fast cell-type identification using scRNA-seq data and a comprehensive cell marker database. ScType provides unbiased and accurate cell type annotations by ensuring the specificity of marker genes across cell clusters and types. It can also distinguish between healthy and malignant cell populations based on single-nucleotide variant calling.
NATURE COMMUNICATIONS
(2022)
Review
Genetics & Heredity
Matthew J. Rybin, Melina Ramic, Natalie R. Ricciardi, Philipp Kapranov, Claes Wahlestedt, Zane Zeier
Summary: Genome instability is a known feature of various human diseases, with new techniques for detecting DNA damage emerging recently. These tools show promising potential for studying neurodegenerative diseases.
FRONTIERS IN GENETICS
(2021)
Article
Immunology
Chunlin Wang, Klarke M. Sample, Babu Gajendran, Philipp Kapranov, Wuling Liu, Anling Hu, Eldad Zacksenhaus, Yanmei Li, Xiaojiang Hao, Yaacov Ben-David
Summary: The study identified FLI1 as a key transcriptional regulator of WAS and its binding partner WIP in regulating megakaryocyte differentiation. WASP and N-WASP cooperatively control megakaryocytic cell fate, with distinct effects on leukemic cell proliferation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yue Chen, Fei Qi, Fan Gao, Huifen Cao, Dongyang Xu, Kourosh Salehi-Ashtiani, Philipp Kapranov
Summary: This study identified a naturally occurring ribozyme in humans through a genome-wide approach, revealing its evolutionary path and potential functional role in vivo.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biology
Huifen Cao, Dongyang Xu, Ye Cai, Xueer Han, Lu Tang, Fan Gao, Yao Qi, DingDing Cai, Huifang Wang, Maxim Ri, Denis Antonets, Yuri Vyatkin, Yue Chen, Xiang You, Fang Wang, Estelle Nicolas, Philipp Kapranov
Summary: This study provides strong evidence for the regulatory role of the vlincRNA class of lncRNAs, demonstrating their importance in cellular function regulation and their potential role in maintaining genome stability.
Article
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-Ishiyamas, Shohei Noma, Shuhei Noguchi, Takeya Kasukawa, Akira Hasegawa, Harukazu Suzuki, Hiromi Nishiyori-Sueki, Martin C. Frith, Clement Chatelain, Piero Carninci, Michiel J. L. de Hoom, Wyeth W. Wasserman, Laurent Brehelin, Charles-Henri Lecellieree
Summary: The FANTOM5 consortium used CAGE technology to map transcription start sites, finding that a large portion of non-coding transcription initiates at microsatellites. They developed Cap Trap RNA-seq to confirm this transcription, and trained deep learning models to predict CAGE signal at STRs with high accuracy. These models revealed the importance of STR surrounding sequences for distinguishing STR classes and predicting transcription initiation levels.
NATURE COMMUNICATIONS
(2021)
Review
Genetics & Heredity
Huifen Cao, Philipp Kapranov
Summary: This article reviews the significant progress made in the past decade in mapping RNA interactions, validating novel interactions, and interpreting the data obtained using interactome mapping methods.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Ye Cai, Huifen Cao, Fang Wang, Yufei Zhang, Philipp Kapranov
Summary: This study presents a high-resolution method, SSiNGLe-AP, to map abasic (AP) sites in mammalian genomes. The results show that AP sites are nonrandomly distributed in the genome and are influenced by gene expression, age, and tissue type.
NATURE COMMUNICATIONS
(2022)
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)
Review
Genetics & Heredity
Dongyang Xu, Lu Tang, Philipp Kapranov
Summary: Studies using highly sensitive targeted RNA enrichment methods have shown that there is still a large portion of the human transcriptome to be discovered, and that most of the genome is transcribed in a complex, interleaved fashion. These findings are consistent with single-cell transcriptome profiling endeavors that reveal the existence of multiple novel, cell type-specific transcripts. The review discusses the current status of targeted RNA enrichment techniques, their application to the discovery of novel cell type-specific transcripts, and their impact on our understanding of the human genome and transcriptome.
TRENDS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Dongyang Xu, Lingcong Luo, Yu Huang, Meng Lu, Lu Tang, Yong Diao, Philipp Kapranov
Summary: This study established a high-throughput method based on next-generation sequencing to identify replication start sites of mitochondrial genomes at nucleotide-level resolution. The results revealed complex and highly reproducible patterns of mitochondrial initiation sites, indicating the dynamic nature of replication initiation in different cell types and species. Overall, this work highlights the gaps in our understanding of mitochondrial DNA replication and provides a new avenue for further research on mitochondrial and potentially other genomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Fan Gao, Fang Wang, Huifen Cao, Yue Chen, Yong Diao, Philipp Kapranov
Summary: The human genome contains various noncoding transcripts that have been traditionally categorized into long or small based on their lengths. However, the functions and biological significance of most of these transcripts are still unknown. In this study, a high-throughput assay was developed to test the functionality of small noncoding RNAs (sncRNAs) by overexpressing them in human cells. Surprisingly, a significant fraction of unannotated sncRNAs were found to have biological relevance, challenging the assumption that they are merely degradation products. These findings suggest the potential existence of multiple functional sncRNAs in the small noncoding transcriptome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Fang Wang, Huifen Cao, Qiu Xia, Ziheng Liu, Ming Wang, Fan Gao, Dongyang Xu, Bolin Deng, Yong Diao, Philipp Kapranov
Summary: This study found that current analytical methods have high false positive rates and many sites in the public databases cannot be validated. The majority of true ADAR editing sites in a human cancer cell line are located in non-coding transcripts, while many ADAR editing events in exons of protein-coding mRNAs represent false positives. Further development of analytical techniques is needed to identify the editome in any sample.
Article
Biochemistry & Molecular Biology
Dongyang Xu, Yu Huang, Lingcong Luo, Lu Tang, Meng Lu, Huifen Cao, Fang Wang, Yong Diao, Liudmila Lyubchenko, Philipp Kapranov
Summary: Endogenous single-stranded DNA (essDNA) can form in a mammalian genome and can have both important roles and detrimental consequences to genome integrity. We developed the SSiNGLe-P1 approach to identify essDNA regions in a high-throughput manner. Using this method, we found new evidence for the strand-displacement model in mitochondrial DNA replication and identified functional elements in the nuclear genome that are enriched in essDNA regions, including DNA replication origins, R-loops, and promoters. Additionally, many of the essDNA regions identified have not been annotated and could represent unknown functional elements.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Dongyang Xu, Lu Tang, Junjun Zhou, Fang Wang, Huifen Cao, Yu Huang, Philipp Kapranov
Summary: High-throughput screening methods have identified uncharacterized functional elements in the human genome, including novel exons of known and new genes, which can be massively induced under specific stresses and represent bi-cistronic protein-coding mRNAs.
Article
Biotechnology & Applied Microbiology
Zhonghua Du, Xue Wen, Yichen Wang, Lin Jia, Shilin Zhang, Yudi Liu, Lei Zhou, Hui Li, Wang Yang, Cong Wang, Jingcheng Chen, Yajing Hao, Huiling Chen, Dan Li, Naifei Chen, Ilkay Celik, Yanbo Zhu, Zi Yan, Changhao Fu, Shanshan Liu, Benzheng Jiao, Zhuo Wang, Hui Zhang, Gunhan Gulsoy, Jianjun Luo, Baoming Qin, Sujun Gao, Philipp Kapranov, Miguel A. Esteban, Songling Zhang, Wei Li, Ferhat Ay, Runsheng Chen, Andrew R. Hoffman, Jiuwei Cui, Ji-Fan Hu
Summary: Platr10 is a novel chromatin RNA molecule activated during somatic cell reprogramming, essential for maintaining pluripotency by modulating chromatin architecture and regulating DNA methylation.
