Review
Biochemistry & Molecular Biology
Zongqin Mei, Yahao Mou, Nan Zhang, Xiaoyu Liu, Zuoshun He, Shiyan Gu
Summary: N-6-metyladenosine (m(6)A) is a common RNA methylation modification in mammals and plays regulatory roles in various physiological and pathological processes. This review provides a summary of the specific methyltransferases, demethylases, and methyl-binding proteins involved in m(6)A modification. It also focuses on the roles of m(6)A modification and its regulatory proteins in the production and function of miRNAs in different disease processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Yibo Zhao, Nikoleta A. Vavouraki, Ruth C. Lovering, Valentina A. Escott-Price, Kirsten Harvey, Patrick A. A. Lewis, Claudia Manzoni
Summary: Mutations in LRRK2 gene are the main cause of Parkinson's disease. However, the function of LRRK2 protein is still unclear. This study constructed a protein-protein interactome of LRRK2 and analyzed its expression patterns in different tissue types. It was found that LRRK2 interactors showed distinct expression features in the brain compared to peripheral tissues. The study also identified a potential functional cluster of LRRK2 in the striatum.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria J. R. Bezerra, Danielle M. N. Moura, Eden R. Freire, Fabiola B. Holetz, Christian R. S. Reis, Tallyta T. S. Monteiro, Adriana R. S. Pinto, Ning Zhang, Antonio M. Rezende, Antonio Pereira-Neves, Regina C. B. Q. Figueiredo, Christine Clayton, Mark C. Field, Mark Carrington, Osvaldo P. de Melo Neto
Summary: Translation in pathogenic protozoans of the family Trypanosomatidae involves multiple eIF4F-like complexes, with the EIF4E4/EIF4G3 and EIF4E3/EIF4G4 pairs being the most prominent. These complexes exhibit distinct protein partners and play important roles in gene expression and cell morphology. Knockdown studies revealed that EIF4E3/EIF4G4 are essential for viability and are involved in cytokinesis. The differential association of mRNAs with each complex was also identified through CLIP-seq analysis, further confirming their distinct functions.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Meile Mo, Bihu Liu, Yihuan Luo, Jennifer Hui Juan Tan, Xi Zeng, Xiaoyun Zeng, Dongping Huang, Changhua Li, Shun Liu, Xiaoqiang Qiu
Summary: This study identified three pivotal HCC-related circRNAs and provided novel insights into the underlying mechanisms of the circRNA-miRNA-mRNA regulatory network in HCC.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Plant Sciences
Yan Wu, Wenjun Zha, Dongfeng Qiu, Jianping Guo, Gang Liu, Changyan Li, Bian Wu, Sanhe Li, Junxiao Chen, Liang Hu, Shaojie Shi, Lei Zhou, Zaijun Zhang, Bo Du, Aiqing You
Summary: This study conducted a genome-wide analysis of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in BPH6-transgenic and Nipponbare rice plants before and after brown planthopper (BPH) feeding. A total of 310 lncRNAs and 129 circRNAs were differentially expressed in response to BPH infestation. The potential functions of these lncRNAs and circRNAs as competitive endogenous RNAs (ceRNAs) were predicted and investigated, revealing their involvement in various biological processes such as cell wall organization, developmental growth, and stress response. This study provides insights into the resistance network of rice against BPH and enhances our understanding of the rice-BPH interaction.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Neurosciences
Shilin Jia, JinYue Liu, Yanhao Chu, Qing Liu, Lijia Mai, Wenguo Fan
Summary: The trigeminal ganglion is responsible for processing orofacial sensory information, and the communication between trigeminal ganglion neurons and other cells plays a crucial role in this process. Purinergic signaling, a widespread pathway in intercellular communication, contributes to neuromodulation and orofacial sensation. In this study, single-cell RNA sequencing was performed to identify different cell populations in the trigeminal ganglion and explore the expression patterns of genes associated with purinergic signaling.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
Ming-Wang Zhang, Zhi-Hong Zhu, Zhi-Kuan Xia, Xin Yang, Wan-Ting Luo, Jun-Hong Ao, Rong-Ya Yang
Summary: Invasive Trichosporon asahii infection in immunodeficient hosts often leads to high mortality, but the pathogenesis is still unknown. This study identified a circRNA-associated competing endogenous RNA network during T. asahii infection, shedding light on the interaction between T. asahii and host cells.
MILITARY MEDICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Xiuni Qin, Bo Chen
Summary: In this study, several novel biomarkers that affect the prognosis of neuroblastoma (NB) patients were identified through gene expression analysis, and several of these genes were preliminarily confirmed as potential target genes of MYCN. These findings are expected to become new targets for the treatment of high-risk NB patients.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Shasha Li, Chenyang Lu, Yuan Zhang, Xiaolu Zhao, Kequan Lin, Xiufang Kong, David Fox, Lixiang Xue, Lichao Sun, Yi Liu, Fengbiao Mao
Summary: This study identified 45 carcinogenic autoimmune disease risk (CAD) genes and revealed the enrichment of T cell signaling pathway and B cell signaling pathway. It also found that immune cell signaling was downregulated in renal cancer compared with SLE, while stemness signature was enriched in both renal cancer or lymphoma and SLE in specific subpopulations. The study highlights the common and specific features between ADs and related cancers, and provides insights into new treatments.
Article
Multidisciplinary Sciences
Krishna Neupane, Meng Zhao, Aaron Lyons, Sneha Munshi, Sandaru M. Ileperuma, Dustin B. Ritchie, Noel Q. Hoffer, Abhishek Narayari, Michael T. Woodside
Summary: The RNA pseudoknot of SARS-CoV-2 that induces programmed ribosomal frameshifting is a potential drug target. Through optical tweezer experiments, researchers identified two pseudoknotted conformers with distinct topologies and revealed the folding mechanism of the frameshift signal, shedding light on its conformational heterogeneity and implications for drug discovery based on structure.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Xuanzhe Liu, Huimin Xiao, Xiaotong Peng, Yimin Chai, Shuo Wang, Gen Wen
Summary: This study identified a circRNA-miRNA-mRNA regulatory network in osteoarthritis (OA) and identified three new hub DECs as novel biomarkers for OA.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Jing Li, Bao Shi, Chongnv Wang, Changwei Shao, Xuezhou Liu, Daiqiang Zhang
Summary: Circular RNAs (circRNAs) have emerged as new molecules involved in gene regulation, with tissue-specific patterns of expression and potential roles in various biological processes. This study provides a genome-wide overview of circRNAs in tongue sole tissues during different ovarian developmental stages. Tissue-specific expression of circRNAs was observed, and some differentially expressed circRNAs were validated through qRT-PCR. Additionally, pathway analyses indicate that circRNAs may play essential roles in the ovarian development and maturation of tongue sole.
Article
Biochemistry & Molecular Biology
Bin Zheng, Sarah Gold, Marta Iwanaszko, Benjamin Charles Howard, Lu Wang, Ali Shilatifard
Summary: Bromodomains of BRD4 are not necessary for Pol II pause release, instead, a C-terminal motif that interacts with PTEFb is both necessary and sufficient for this function.
Article
Immunology
Fei Guo, Brandon Hancock, Alec Griffith, Hui Lin, Kaitlyn Howard, Joshua Keegan, Fan Zhang, Adam Chicoine, Laura Cahill, Julie Ng, James Lederer
Summary: This study comprehensively characterized injury-responsive Tregs in mice using multi-dimensional profiling techniques, and found that CD44(high) Tregs expand and exhibit a highly suppressive ability in response to injury, distinct from CD44(low) Tregs. Injury-induced upregulation of specific genes was observed in CD44(high) Tregs, with chemokine receptors and cell division being the most enriched functional terms in this population.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Uri Seroussi, Andrew Lugowski, Lina Wadi, Robert X. Lao, Alexandra R. Willis, Winnie Zhao, Adam E. Sundby, Amanda G. Charlesworth, Aaron W. Reinke, Julie M. Claycomb
Summary: In this study, the researchers systematically analyzed each C. elegans Argonaute (AGO) using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG tags. They characterized the expression patterns, identified small RNA binding complements, and determined the effects of ago loss on small RNA populations and developmental phenotypes. The analysis revealed distinct regulatory modules and novel stress-induced fertility and pathogen response phenotypes due to ago loss.
Article
Immunology
Elina A. Tuovinen, Sakari Poysti, Firas Hamdan, Kim My Le, Salla Keskitalo, Tanja Turunen, Lea Minier, Nanni Mamia, Kaarina Heiskanen, Markku Varjosalo, Vincenzo Cerullo, Juha Kere, Mikko R. J. Seppanen, Arno Hanninen, Juha Gronholm
Summary: This study investigated the function and phenotype of expanded gamma delta T cells in individuals with atypical SCID. The findings suggest that these cells have distinct characteristics in terms of IL2RG cell surface expression, signaling, cytotoxicity, and the presence of a novel IL2RG variant restricted to gamma delta T cells.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Elina A. Tuovinen, Outi Kuismin, Leila Soikkonen, Timi Martelius, Meri Kaustio, Sari Hamalainen, Hanna Viskari, Jaana Syrjanen, Ulla Wartiovaara-Kautto, Kari K. Eklund, Janna Saarela, Markku Varjosalo, Juha Kere, Timo Hautala, Mikko R. J. Seppanen
Summary: The NF-κB family of transcription factors is important in cellular signaling pathways, and NFKB1 variants have been associated with CVID and immunodeficiency. However, the penetrance and prevalence of CVID are relatively low, while inflammatory manifestations are more common.
CLINICAL IMMUNOLOGY
(2023)
Article
Microbiology
Mirka Lampi, Pavlina Gregorova, M. Suleman Qasim, Niklas C. V. Ahlblad, L. Peter Sarin
Summary: This study provides the first comprehensive quantitative characterization of the tRNA modificome in the marine bacterium Shewanella glacialimarina during Shewanella phage 1/4 infection, shedding light on the temporal dynamics of infection-induced changes to the tRNA modification landscape. The study reveals that tRNA modifications can be grouped into distinct categories based on modification level changes at different infection stages. Furthermore, a correlation between phage codon usage and PTM modification is suggested, as queuosine modification appears exclusively on tRNAs with GUN anticodons in viral transcripts expressed at the late stage of infection. This work lays the foundation for further investigations into RNA-based regulatory mechanisms employed by bacteriophages to control prokaryotic translation machinery.
Review
Biochemistry & Molecular Biology
Alba Coego, Helena Covelo-Molares, Diana Guallar
Summary: Ageing is a natural biological process characterized by the gradual decline of physiological functions. Recent studies have shown that RNA modifications play a role in regulating ageing and age-related diseases. Transcriptome analysis has revealed changes in RNA modifications in neurodegenerative diseases and the expression of RNA modifiers with age. This research highlights the potential role of RNA modifications as novel regulators of ageing and provides new avenues for treating age-related diseases.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Larisa Chernyaeva, Giorgio Ratti, Laura Teirila, Satoshi Fudo, Uni Rankka, Anssi Pelkonen, Paula Korhonen, Katarzyna Leskinen, Salla Keskitalo, Kari Salokas, Christina Gkolfinopoulou, Katrina E. Crompton, Matti Javanainen, Lotta Happonen, Markku Varjosalo, Tarja Malm, Ville Leinonen, Angeliki Chroni, Paivi Saavalainen, Seppo Meri, Tommi Kajander, Adam J. M. Wollman, Eija Nissila, Karita Haapasalo
Summary: By studying the interaction between apoE4 and FH, it was found that this interaction affects the neurotoxicity and clearance of A beta 1-42, which is related to AD pathogenesis. ApoE and FH reduce the binding of A beta 1-42 to CR3 and the subsequent phagocytosis by microglia, leading to changes in gene expression related to AD. FH forms complement-resistant oligomers with apoE/A beta 1-42 complexes, and the formation of these complexes is isoform specific, with apoE2 and apoE3 having higher affinity to FH than apoE4. These complexes reduce A beta 1-42 oligomerization and toxicity, and colocalize with C1q on A beta plaques in the brain, providing important insights into AD pathogenesis and how the strongest genetic risk factor for AD predisposes to neuroinflammation in the early stages of the disease pathology.
Article
Biochemistry & Molecular Biology
Yosuke Senju, Toiba Mushtaq, Helena Vihinen, Aki Manninen, Juha Saarikangas, Katharina Ven, Ulrike Engel, Markku Varjosalo, Eija Jokitalo, Pekka Lappalainen
Summary: The MTSS1 protein binds to the Arp2/3 and WAVE-2 protein complexes, promoting the formation of dynamic membrane folds at cell-cell junctions and enhancing the integrity of these junctions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Oncology
Sini Luoma, Philipp Sergeev, Komal Kumar Javarappa, Tiina J. Ohman, Markku Varjosalo, Marjaana Saily, Pekka Anttila, Marja Sankelo, Anu Partanen, Anne Nihtinen, Caroline A. A. Heckman, Raija Silvennoinen
Summary: The bone marrow microenvironment plays a significant role in cancer survival and immune evasion in multiple myeloma (MM). By analyzing longitudinal bone marrow samples, researchers found distinct immune profiles between patients with good and bad responses to specific treatment. These findings suggest that deep immune profiling could be a useful tool for treatment guidance and require further investigation.
Article
Multidisciplinary Sciences
Lisa Gawriyski, Eeva-Mari Jouhilahti, Masahito Yoshihara, Liangru Fei, Jere Weltner, Tomi T. Airenne, Ras Trokovic, Shruti Bhagat, Mari H. Tervaniemi, Yasuhiro Murakawa, Kari Salokas, Xiaonan Liu, Sini Miettinen, Thomas R. Burglin, Biswajyoti Sahu, Timo Otonkoski, Mark S. Johnson, Shintaro Katayama, Markku Varjosalo, Juha Kere
Summary: LEUTX, a transcription factor, is expressed in human preimplantation embryos at the 4-8 cell stages and silenced in somatic tissues. Through multiomic characterization, we found that LEUTX interacts with histone acetyltransferases, EP300 and CBP, via its 9 amino acid transactivation domain. It targets genomic cis-regulatory sequences overlapping with repetitive elements and functions as a transcriptional activator, upregulating genes involved in preimplantation development and 8-cell-like markers.
Editorial Material
Biochemical Research Methods
Salla Keskitalo, Markku Varjosalo
EXPERT REVIEW OF PROTEOMICS
(2023)
Article
Multidisciplinary Sciences
Svetlana Konovalova, Ruben Torregrosa-Munumer, Pooja Manjunath, Xiaonan Liu, Sundar Baral, Kaneez Fatima, Minna Holopainen, Jouni Kvist, Jayasimman Rajendran, Yang Yang, Markku Varjosalo, Reijo Kakela, Pentti Somerharju, Henna Tyynismaa
Summary: NERCLIN is a small mitochondrial protein that negatively regulates CL homeostasis and mitochondrial ultrastructure. It interacts with the CL synthesis and prohibitin complexes to regulate CL content and contributes to stress-induced adaptation of mitochondrial dynamics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Matias Kinnunen, Xiaonan Liu, Elina Niemelae, Tiina Oehman, Lisa Gawriyski, Kari Salokas, Salla Keskitalo, Markku Varjosalo
Summary: Gene fusions can produce chimeric fusion proteins that have unpredictable properties, some of which can function as oncogenic drivers. ETV6-NTRK3 is a fusion gene that produces a constitutively active fusion kinase. Through proximity labeling, a study was conducted to analyze the interactomes of all four known ETV6-NTRK3 variants, revealing similarities and differences in their interacting proteins. These findings may explain the differences in reported frequencies and tissue specificities of the ETV6-NTRK3 variants.
Review
Oncology
Kari Salokas, Giovanna Dashi, Markku Varjosalo
Summary: Cancer-associated gene fusions, known as oncofusions, are driving forces in oncogenesis and have revolutionized cancer research through advanced sequencing technologies. They manipulate cellular signaling pathways and show promise as targets for therapy and diagnostic markers. Further research is needed to understand their functional impact and harness their potential for precision cancer treatment.
Article
Cell Biology
Emilia Piki, Alice Dini, Juuli Raivola, Kari Salokas, Kaiyang Zhang, Markku Varjosalo, Teijo Pellinen, Katja Valimaki, Kristina Tabor Veskimae, Synnove Staff, Sampsa Hautaniemi, Astrid Murumagi, Daniela Ungureanu
Summary: Dysregulation of the Wnt pathway, specifically the expression of the non-canonical receptor ROR1, is linked to ovarian cancer progression and drug resistance. ROR1 expression is enhanced by neoadjuvant chemotherapy, and its interaction with Wnt5a activates oncogenic signaling pathways in ovarian cancer cells. Furthermore, ROR1 and its downstream effector STAT3 are expressed at higher levels in stromal cells than in epithelial cancer cells in ovarian cancer tumors.
CELL DEATH DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Liang Wang, Taru Hilander, Xiaonan Liu, Hoi Ying Tsang, Ove Eriksson, Christopher B. Jackson, Markku Varjosalo, Hongxia Zhao
Summary: This study identifies GTPBP8 as a crucial factor in the assembly of the mitoribosomal large subunit (mt-LSU) and mitochondrial translation. Depletion of GTPBP8 leads to abnormal accumulation of mt-LSU and compromised mitochondrial function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Genetics & Heredity
Susanna Nousiainen, Outi Kuismin, Siiri Reinikka, Roosa Manninen, Sara Khamaiseh, Mari Kuivalainen, Anna Terho, Sari Koivurova, Maarit Niinimaki, Kari Salokas, Markku Varjosalo, Anne Ahtikoski, Ralf Butzow, Outi Lindgren, Outi Uimari, Pia Vahteristo
Summary: In this study, FGFR4, NALCN, and NAV2 were identified as novel high-risk candidate genes for familial endometriosis. The findings also support the association between endometriosis and high-grade serous carcinoma.