Article
Biotechnology & Applied Microbiology
Chenxiao Xue, Caixia Cao
Summary: By using CRISPR-Cas base editing and prime editing, we manipulated upstream open reading frames - eukaryotic translational control elements - in rice to regulate translation levels. This enabled predictable and desired downregulation of gene expression, leading to quantitative phenotypic changes and crop improvement.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kommireddy Vasu, Iyappan Ramachandiran, Aayushi Chechi, Krishnendu Khan, Debjit Khan, Randall Kaufman, Paul L. Fox
Summary: Adiponectin, a secretory protein encoded by the ADIPOQ gene, plays a causal role in insulin resistance. Anti-diabetic drugs can increase the levels of adiponectin in the blood, enhancing insulin sensitivity through a post-transcriptional mechanism. This study found that a regulatory sequence called uORF in the Adipoq mRNA has an inhibitory effect on its translation. Disruption of uORF in adipocytes increased adiponectin expression, altered lipid metabolism, and inhibited the response of other tissues to adiponectin.
Article
Genetics & Heredity
Ty A. Bottorff, Heungwon Park, Adam P. Geballe, Arvind Rasi Subramaniam
Summary: Upstream open reading frames (uORFs) are present in over half of all human mRNAs and can regulate the translation of downstream open reading frames through various mechanisms. A study found that ribosome stalling in the first encountered uORF can prevent decreases in protein expression when ribosome loading onto mRNA is reduced. This buffering mechanism is insensitive to the location of the ribosome stall, and computational modeling suggests that colliding ribosomes dissociate rather than queue on the mRNA molecule.
Article
Plant Sciences
Barry Causier, Tayah Hopes, Mary McKay, Zachary Paling, Brendan Davies
Summary: The regulation of protein synthesis is crucial for the growth and development of organisms. Conserved peptide uORFs (CPuORFs), a rare subset of uORFs, have been found to conditionally regulate translation. This study demonstrates that certain CPuORFs in Arabidopsis can regulate the translation of downstream ORFs in response to heat stress and water limitation, suggesting their versatile applications.
PLANT CELL AND ENVIRONMENT
(2022)
Article
Biochemistry & Molecular Biology
Zhiyong Li, Yajuan Fu, Jinyu Shen, Jiansheng Liang
Summary: WNK8 gene expression is post-transcriptionally regulated through an upstream open reading frame (uORF) in its 5' untranslated region, causing ribosome stalling. WNK8 and its downstream target RACK1 synergistically coordinate ABA signaling rather than antagonistically modulating glucose response and flowering.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Plant Sciences
Miryam A. Cymerman, Helen Saul, Ronit Farhi, Karina Vexler, Dror Gottlieb, Irina Berezin, Orit Shaul
Summary: Translated upstream open reading frames (uORFs) can inhibit the translation of main open reading frames (ORFs) and lead to transcript degradation in eukaryotic cells. In mammalian cells, the length, structure, and reinitiation efficiency of translated uORFs play important roles in determining whether the transcripts will be targeted for degradation by the nonsense-mediated mRNA decay (NMD) pathway. However, the significance of these factors in NMD targeting for plants is still not well-studied.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Article
Cell Biology
Thao P. Phan, Christina A. Boatwright, Chelsea G. Drown, Marnie W. Skinner, Margaret A. Strong, Philip W. Jordan, Andrew J. Holland
Summary: This study reveals the translational control of PLK4 through uORFs and its crucial role in preventing centriole amplification and preserving genomic integrity in germ cells. Knockout of Plk4 uORFs leads to reduced fertility and increased mitotic errors in mice, which can be rescued by reducing Plk4 mRNA levels. These findings highlight the importance of uORF-mediated translational suppression of PLK4 in maintaining proper cell division and preventing disease progression.
GENES & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Lara Juergens, Felix Manske, Elvira Hubert, Tabea Kischka, Lea Floetotto, Oliver Klaas, Victoria Shabardina, Christoph Schliemann, Wojciech Makalowski, Klaus Wethmar
Summary: This study analyzed genetic variations in patient samples from various cancers and found that 66.5% of samples were affected by somatic single nucleotide variants in uORFs. These variants altered uAUG, uStop, and aTIS codons, with functional evaluation showing significant translational deregulation caused by 19 uORF variants.
Review
Cardiac & Cardiovascular Systems
Omar Soukarieh, Caroline Meguerditchian, Carole Proust, Dylan Aissi, Melanie Eyries, Aurelie Goyenvalle, David-Alexandre Tregouet
Summary: HTS technologies are transforming research and molecular diagnostics by exploring millions of nucleotide sequences, focusing on identifying genetic variations contributing to rare and common human diseases. The study highlights the importance of 5'UTR variants altering upORFs and their association with rare cardiovascular disorders.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Geriatrics & Gerontology
Alexandros Frydas, Rita Cacace, Julie van der Zee, Christine Van Broeckhoven, Eline Wauters
Summary: Genetic variants within the uORF regions of the GRN gene may alter PGRN expression levels and contribute to frontotemporal lobar degeneration. The functional uORFs present in the alternative 5' UTR act as potential regulators of PGRN expression, indicating a role for genetic variation in modulating gene function.
NEUROBIOLOGY OF AGING
(2022)
Article
Cell Biology
Ying Yang, Damian Gatica, Xu Liu, Runliu Wu, Rui Kang, Daolin Tang, Daniel J. Klionsky
Summary: This study reports the role of uORF-mediated translational control in regulating multiple Atg proteins in yeast and human cells. These findings suggest that uORF-mediated translational control is a widely used mechanism among ATG genes and provide a model for how some ATG genes bypass translational suppression under stress conditions to maintain proper autophagy levels.
Article
Plant Sciences
Ho-Wei Wu, Erickson Fajiculay, Jing-Fen Wu, Ching-Cher Sanders Yan, Chao-Ping Hsu, Shu-Hsing Wu
Summary: Upstream open reading frames (uORFs) are commonly found in eukaryotic messenger RNAs and can achieve low but precise protein production by repressing the translation efficiency of downstream coding sequences. These uORFs can buffer protein production levels in the plant circadian clock, contributing to its robust operation.
Article
Microbiology
Gauthier Roy, Rudy Antoine, Annie Schwartz, Stephanie Slupek, Alex Rivera-Millot, Marc Boudvillain, Francoise Jacob-Dubuisson
Summary: Copper is a necessary transition metal for living beings but also highly toxic, and bacteria tightly control its homeostasis through transcriptional regulators. In this study, a new control mechanism mediated by a small protein called CruR, for copper-responsive upstream regulator, was identified in Bordetella pertussis. CruR is able to perceive intracellular copper while being translated by the ribosome, which shuts down the transcription of downstream genes responsible for copper uptake. This posttranscriptional regulation mechanism limits copper import in conditions where it is abundant for the bacterium. Homologs of CruR genes are found in many bacteria, suggesting that the regulatory function unveiled here is likely a general property of this new protein family.
Article
Cell Biology
Albertas Navickas, Hosseinali Asgharian, Juliane Winkler, Lisa Fish, Kristle Garcia, Daniel Markett, Martin Dodel, Bruce Culbertson, Sohit Miglani, Tanvi Joshi, Keyi Yin, Phi Nguyen, Steven Zhang, Nicholas Stevers, Hun-Way Hwang, Faraz Mardakheh, Andrei Goga, Hani Goodarzi
Summary: Cancer cells exploit post-transcriptional regulatory mechanisms to achieve abnormal expression of gene networks driving metastasis. The role of translational control in cancer progression is not well understood. Using ribosome profiling, researchers compared translation efficiencies in poorly and highly metastatic breast cancer cells and patient-derived xenografts, identifying HNRNPC as a translational controller of a specific mRNA regulon. Downregulation of HNRNPC in highly metastatic cells leads to lengthening of the 3' untranslated region of HNRNPC-bound mRNAs and subsequent translational repression. Modulating HNRNPC expression affects the metastatic capacity of breast cancer cells and reduced HNRNPC expression is associated with worse prognosis in breast cancer patients.
NATURE CELL BIOLOGY
(2023)
Article
Clinical Neurology
Shaoping Zhong, Yangye Lian, Wenyi Luo, Rongkui Luo, Xiaoling Wu, Jun Ji, Yuan Ji, Jing Ding, Xin Wang
Summary: NIID is a neurodegenerative disease characterized by widespread inclusions, and recent research has identified a GGC repeat expansion in the 5'UTR of NOTCH2NLC gene associated with the disease. This expansion triggers the translation of a polyglycine protein, N2NLCpolyG, which tends to aggregate and impair nuclear lamina and nucleocytoplasmic transport without causing immediate neuronal cell death. These findings suggest a similarity in pathogenic mechanisms between NIID and other GGC-repeat diseases.
ACTA NEUROPATHOLOGICA
(2021)
Article
Biochemistry & Molecular Biology
Takafumi Mashiko, Eiji Sakashita, Katsumi Kasashima, Kaoru Tominaga, Kenji Kuroiwa, Yasuyuki Nozaki, Tohru Matsuura, Toshiro Hamamoto, Hitoshi Endo
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Multidisciplinary Sciences
Naoki Iwamori, Kaoru Tominaga, Tetsuya Sato, Kevin Riehle, Tokuko Iwamori, Yasuyuki Ohkawa, Cristian Coarfa, Etsuro Ono, Martin M. Matzuk
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2016)
Review
Pharmacology & Pharmacy
Kaoru Tominaga, Olivia M. Pereira-Smith
CURRENT DRUG TARGETS
(2012)
Article
Oncology
AndreAna N. Pena, Kaoru Tominaga, Olivia M. Pereira-Smith
EXPERIMENTAL CELL RESEARCH
(2011)
Article
Clinical Neurology
Syuichi Tetsuka, Kaoru Tominaga, Eriko Ohta, Kenji Kuroiwa, Eiji Sakashita, Katsumi Kasashima, Toshiro Hamamoto, Michito Namekawa, Mitsuya Morita, Shinsuke Natsui, Tatsuo Morita, Keiko Tanaka, Yoshihisa Takiyama, Imaharu Nakano, Hitoshi Endo
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2013)
Article
Geriatrics & Gerontology
Viviana I. Perez, Lisa A. Cortez, Christie M. Lew, Marisela Rodriguez, Celeste R. Webb, Holly Van Remmen, Asish Chaudhuri, Wenbo Qi, Shuko Lee, Alex Bokov, Wilson Fok, Dean Jones, Arlan Richardson, Junji Yodoi, Yiqiang Zhang, Kaoru Tominaga, Gene B. Hubbard, Yuji Ikeno
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2011)
Article
Cell & Tissue Engineering
Meizhen Chen, Olivia M. Pereira-Smith, Kaoru Tominaga
STEM CELL RESEARCH
(2011)
Article
Biochemical Research Methods
Satoshi Yamamoto, Yasumitsu Nagao, Kenji Kuroiwa, Yoji Hakamata, Masaru Ichida, Fumiko Saito-Ohara, Kaoru Tominaga, Hitoshi Endo
TRANSGENIC RESEARCH
(2014)
Article
Multidisciplinary Sciences
Satsuki Miyata, Kaoru Tominaga, Eiji Sakashita, Masashi Urabe, Yoshiyuki Onuki, Akira Gomi, Takashi Yamaguchi, Makiko Mieno, Hiroaki Mizukami, Akihiro Kume, Keiya Ozawa, Eiju Watanabe, Kensuke Kawai, Hitoshi Endo
SCIENTIFIC REPORTS
(2019)
Article
Multidisciplinary Sciences
Rintaro Kuroda, Kaoru Tominaga, Katsumi Kasashima, Kenji Kuroiwa, Eiji Sakashita, Hiroko Hayakawa, Tom Kouki, Nobuhiko Ohno, Kensuke Kawai, Hitoshi Endo
Summary: Mitochondrial dysfunction caused by Tfam inactivation in neural stem cells impairs respiratory chain activities, leading to deficits in neural differentiation and maturation in both in vivo and in vitro settings. This dysfunction triggers an integrated stress response that may protect against neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Kaoru Tominaga, Eiji Sakashita, Katsumi Kasashima, Kenji Kuroiwa, Yasumitsu Nagao, Naoki Iwamori, Hitoshi Endo
Summary: Epigenetic factors play a crucial role in establishing functional organ systems during development, including brain development. However, the precise mechanism of epigenetic regulation in brain development and neurogenesis remains largely unknown. In this study, the researchers discovered the critical role of the Tip60 protein in brain development and the maintenance and function of neural stem/progenitor cells (NSCs). Tip60 deficiency led to multiple abnormalities in brain development, including microcephaly, reduced proliferation of developing brain cells, and impaired neural differentiation and migration. The study also revealed that Tip60 is involved in the transition from neurogenesis to gliogenesis during brain development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Genetics & Heredity
Meizhen Chen, Kaoru Tominaga, Jungmi Ahn, Michael Foret, Naoki Iwamori, Martin M. Matzuk, Paul R. Mueller, Gary O. Gaufo
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2015)
Meeting Abstract
Clinical Neurology
Syuichi Tetsuka, Kaoru Tominaga, Kenji Kuroiwa, Mitsuya Morita, Hitoshi Endo
ANNALS OF NEUROLOGY
(2013)
Article
Oncology
Griselda Martrat, Christopher A. Maxwell, Emiko Tominaga, Montserrat Porta-de-la-Riva, Nuria Bonifaci, Laia Gomez-Baldo, Massimo Bogliolo, Conxi Lazaro, Ignacio Blanco, Joan Brunet, Helena Aguilar, Juana Fernandez-Rodriguez, Sheila Seal, Anthony Renwick, Nazneen Rahman, Julia Kuehl, Kornelia Neveling, Detlev Schindler, Maria J. Ramirez, Maria Castella, Gonzalo Hernandez, Douglas F. Easton, Susan Peock, Margaret Cook, Clare T. Oliver, Debra Frost, Radka Platte, D. Gareth Evans, Fiona Lalloo, Rosalind Eeles, Louise Izatt, Carol Chu, Rosemarie Davidson, Kai-Ren Ong, Jackie Cook, Fiona Douglas, Shirley Hodgson, Carole Brewer, Patrick J. Morrison, Mary Porteous, Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Gaia Roversi, Monica Barile, Alessandra Viel, Barbara Pasini, Laura Ottini, Anna Laura Putignano, Antonella Savarese, Loris Bernard, Paolo Radice, Sue Healey, Amanda Spurdle, Xiaoqing Chen, Jonathan Beesley, Matti A. Rookus, Senno Verhoef, Madeleine A. Tilanus-Linthorst, Maaike P. Vreeswijk, Christi J. Asperen, Danielle Bodmer, Margreet G. E. M. Ausems, Theo A. van Os, Marinus J. Blok, Hanne E. J. Meijers-Heijboer, Frans B. L. Hogervorst, David E. Goldgar, Saundra Buys, Esther M. John, Alexander Miron, Melissa Southey, Mary B. Daly, Katja Harbst, Ake Borg, Johanna Rantala, Gisela Barbany-Bustinza, Hans Ehrencrona, Marie Stenmark-Askmalm, Bella Kaufman, Yael Laitman, Roni Milgrom, Eitan Friedman, Susan M. Domchek, Katherine L. Nathanson, Timothy R. Rebbeck, Oskar Thor Johannsson, Fergus J. Couch, Xianshu Wang, Zachary Fredericksen, Daniel Cuadras, Vctor Moreno, Friederike K. Pientka, Reinhard Depping, Trinidad Caldes, Ana Osorio, Javier Benitez, Juan Bueren, Tuomas Heikkinen, Heli Nevanlinna, Ute Hamann, Diana Torres, Maria Adelaide Caligo, Andrew K. Godwin, Evgeny N. Imyanitov, Ramunas Janavicius, Olga M. Sinilnikova, Dominique Stoppa-Lyonnet, Sylvie Mazoyer, Carole Verny-Pierre, Laurent Castera, Antoine de Pauw, Yves-Jean Bignon, Nancy Uhrhammer, Jean-Philippe Peyrat, Philippe Vennin, Sandra Fert Ferrer, Marie-Agnes Collonge-Rame, Isabelle Mortemousque, Lesley McGuffog, Georgia Chenevix-Trench, Olivia M. Pereira-Smith, Antonis C. Antoniou, Julian Ceron, Kaoru Tominaga, Jordi Surralles, Miguel Angel Pujana
BREAST CANCER RESEARCH
(2011)
Article
Biochemistry & Molecular Biology
A. Prabakaran, Amit Alexander
Summary: The molecular interactions and mucoadhesive nature of chitosan-coated liposomes with mucin are crucial for the development of an effective drug delivery system. The positively charged SA-CH-LPs showed stronger interaction and better mucoadhesive properties compared to negatively charged SALPs, thereby improving drug retention in the nasal cavity and enhancing therapeutic efficacy.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)
Article
Biochemistry & Molecular Biology
Maryam Noei-Khesht Masjedi, Esmaeil Sadroddiny, Jafar Ai, Saeed Balalaie, Yazdan Asgari
Summary: This study discovered an effective strategy for cargo sorting within exosomes by incorporating an appropriate cleavage site, providing further insight into the potential of exosomes as nano-shuttles bearing therapeutic biomolecules.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)
Article
Biochemistry & Molecular Biology
Pei -Gee Yap, Chee-Yuen Gan
Summary: This study collected the sequences of 128 tyrosinase inhibitory peptides and analyzed their hydrophobicity/hydrophilicity properties and amino acid profiles. Molecular docking analysis was used to investigate the binding interactions between peptides and tyrosinase. The study found that hydrophobic and/or polar neutral properties facilitate or stabilize peptide binding with tyrosinase, and short peptides with cysteine and tyrosine tend to bind to the active site of tyrosinase. These findings provide detailed explanations for the relationship between peptide/amino acid structures and tyrosinase inhibition, as well as potential anti-melanogenesis mechanisms for peptide-based treatments against skin hyperpigmentation.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)
Article
Biochemistry & Molecular Biology
Ye Yang, Hai-Lian Chen, Su Fang Wu, Wei Bao
Summary: The study found that CHMP4B and VPS4A play an important role in reversing GSDMD-mediated pyroptosis by facilitating cell membrane remodeling in endometrial carcinoma.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)
Article
Biochemistry & Molecular Biology
Aya Al Othman, Dmitry Bagrov, Julian M. Rozenberg, Olga Glazova, Gleb Skryabin, Elena Tchevkina, Alexandre Mezentsev, Mikhail Durymanov
Summary: Arc protein is found in glutamatergic neurons of vertebrates and can be transferred between neurons in extracellular vesicles (EVs). In glioma cells, Arc protein is also present in EVs and can facilitate the transfer of mRNA, potentially contributing to tumor progression and affecting synaptic plasticity in cancer patients.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)
Article
Biochemistry & Molecular Biology
Nan Zhang, Meng-yu Shen, Qing-li Meng, Hao-ping Sun, Fang-yi Fan, Hai Yi, Yong-jian Yang
Summary: In this study, it was demonstrated for the first time that FAT1 inhibited AML proliferation by reducing autophagy level. FAT1 achieved this by decreasing the expression of ATG4B, which is related to autophagy. Mechanistically, FAT1 decreased the levels of phosphorylated and intranuclear smad2/3, thus decreasing the activity of the ATG4B gene promoter. It was also found that FAT1 competitively bound to TGF-beta R II, leading to reduced phosphorylation of TGF-beta R I and smad2/3. Knockdown of FAT1 promoted AML autophagy and proliferation in vivo.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)
Article
Biochemistry & Molecular Biology
Oleh Demianchuk, Myroslava Vatashchuk, Dmytro Gospodaryov, Viktoria Hurza, Marian Ivanochko, Vitalii Derkachov, Vladyslav Berezovskyi, Oleh Lushchak, Kenneth B. Storey, Maria Bayliak, Volodymyr I. Lushchak
Summary: This study investigated the effects of a high-fat high-fructose diet (HFFD) on the behavior, energy metabolism, and oxidative stress markers in the cerebral cortex of mice. The results showed that HFFD stimulated locomotion and defecation, while an AKG-supplemented diet had a tendency to promote anxiety-like behavior. Additionally, there were significant differences in glutathione-dependent detoxification and processes related to autophagy between the two diets.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)
Article
Biochemistry & Molecular Biology
Yusaku Chukai, Ginga Ito, Yasuo Miki, Koichi Wakabayashi, Ken Itoh, Eriko Sugano, Hiroshi Tomita, Tomokazu Fukuda, Taku Ozaki
Summary: The study found that mitochondrial calpain-5 plays an important role in the occurrence and development of ischemia-reperfusion injury and is expressed in the human and mouse brains. Targeting the expression or activity of mitochondrial calpain-5 may have significant implications for suppressing inflammation during I/R injuries such as cerebrovascular diseases.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)
Article
Biochemistry & Molecular Biology
Aline Dias da Purificaca, Victor Debbas, Leonardo Yuji Tanaka, Gabriele Veronica de Mello Gabriel, Joao Wosniak Junior, Tiphany Coralie De Bessa, Sheila Garcia-Rosa, Francisco Rafael Martins Laurindo, Percillia Victoria Santos Oliveira
Summary: The ER transmembrane chaperones DNAJB12 and DNAJB14 play important roles in protein folding and ER stress response. They are regulated by thiol redox processes and are involved in ER protein reflux.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)
Article
Biochemistry & Molecular Biology
Ekaterina O. Bryanskaya, Andrey Y. Vinokurov, Angelina I. Dolgikh, Andrey Dunaev, Plamena R. Angelova, Andrey Y. Abramov
Summary: FAD autofluorescence in cells can assess enzymatic activity, and its intensity variations may be related to different cell types and tissues. High levels of FAD autofluorescence can indicate cell pathology and potentially predict the occurrence of apoptosis and necrosis.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)
Article
Biochemistry & Molecular Biology
Rumei Luan, Manyu Luo, Dongyan Ding, Xin Su, Junling Yang
Summary: Zinc deficiency can worsen obesity-related lung damage, and Nrf2 activation is one of the important mechanisms of this protective effect. Regulating zinc homeostasis can contribute to the prevention and treatment of obesity-related lung injury.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2024)