Universal features of Nsp1-mediated translational shutdown by coronaviruses
Schubert et al. discovered that Nsp1 proteins from different coronaviruses, including MERS-CoV, bind to the ribosomal mRNA channel to inhibit translation. The N-terminal domain of Nsp1 from a bat coronavirus was visualized bound to the decoding center, suggesting a mechanism for the preferential translation o f viral RNAs. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Katharina Schubert, Evangelos D. Karousis, Ivo Ban, Christopher P. Lapointe, Marc Leibundgut, Emilie B äumlin, Eric Kummerant, Alain Scaiola, Tanja Schönhut, Jana Ziegelmüller, Joseph D. Puglisi, Oliver Mühlemann, Nenad Ban Tags: Article Source Type: research
Negative DNA supercoiling induces genome-wide Cas9 off-target activity
Newton et al. demonstrate that changes in DNA structure dramatically reduce the specificity of the gene editing technique CRISPR-Cas9. Underwound (negatively supercoiled) DNA results in off-target activity at thousands of sites across the human genome. This is important to understand for the development of safe and efficient gene editing therapeutics. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Matthew D. Newton, Marialucrezia Losito, Quentin M. Smith, Nishita Parnandi, Benjamin J. Taylor, Pinar Akcakaya, Marcello Maresca, Patrick van Eijk, Simon H. Reed, Simon J. Boulton, Graeme A. King, Maria Emanuela Cuomo, David S. Rueda Tags: Article Source Type: research
Targeting LYPLAL1-mediated cGAS depalmitoylation enhances the response to anti-tumor immunotherapy
Fan et al. report that cGAS undergoes ZDHHC9-mediated palmitoylation to promote its activation, which is antagonized by the acyl-protein thioesterase LYPLAL1. Furthermore, they provide a strategy to augment the cGAS-mediated anti-viral as well as anti-tumor immunity by inhibiting LYPLAL1. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Yizeng Fan, Yang Gao, Li Nie, Tao Hou, Weichao Dan, Zixi Wang, Tianjie Liu, Yi Wei, Yuzhao Wang, Bo Liu, Taotao Que, Yuzeshi Lei, Jin Zeng, Jian Ma, Wenyi Wei, Lei Li Tags: Article Source Type: research
S-acylation of p62 promotes p62 droplet recruitment into autophagosomes in mammalian autophagy
How autophagosomes efficiently sequester phase-separated p62 droplets remains unclear. Huang et al. found a posttranslational modification of p62 with long-chain fatty acids. p62 S-acylation regulates p62 droplet recruitment to the autophagic membrane and selective autophagic flux, thereby contributing to the control of selective autophagic clearance of ubiquitinated proteins. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Xue Huang, Jia Yao, Lu Liu, Jing Chen, Ligang Mei, Jingjing Huangfu, Dong Luo, Xinyi Wang, Changhai Lin, Xiaorong Chen, Yi Yang, Sheng Ouyang, Fujing Wei, Zhuolin Wang, Shaolin Zhang, Tingxiu Xiang, Dante Neculai, Qiming Sun, Eryan Kong, Edward W. Tate, A Tags: Article Source Type: research
An intrinsically disordered region controlling condensation of a circadian clock component and rhythmic transcription in the liver
Zhu et al. report that a core component of the molecular clock, REV-ERBα, forms circadian condensates controlling liver rhythmic gene repression. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Kun Zhu, Isaac J. Celwyn, Dongyin Guan, Yang Xiao, Xiang Wang, Wenxiang Hu, Chunjie Jiang, Lan Cheng, Rafael Casellas, Mitchell A. Lazar Tags: Article Source Type: research
STING channels its proton power
Induction of type I interferon by the STING pathway is a cornerstone of innate immunity. STING also turns on non-canonical autophagy and inflammasome activation although the underlying mechanisms remain ill defined. Liu et al.1 discovered that STING forms a channel that directs proton efflux from the Golgi to drive these responses. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Mingqi Dong, Katherine A. Fitzgerald Tags: Spotlight Source Type: research
How the circadian nuclear orphan receptor REV-ERB α represses transcription: Temporal and spatial phase separation combined
In this issue of Molecular Cell, Zhu et al.1 demonstrate that REV-ERBα and its co-repressor NCOR1 are assembled into daytime-dependent liquid droplets that constitute hubs in which the transcription of multiple REV-ERBα target genes is simultaneously repressed. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Ueli Schibler Tags: Preview Source Type: research
Pulling rank with RNA: RANKL promotes the association of PGC-1 β/RNA complexes with NCoR/HDAC3 to activate gene expression in osteoclasts
In this issue, Abe et al1 report a novel mechanism by which RANKL stimulates osteoclast differentiation and bone resorption through non-coding RNAs that bind PGC-1β and convert the NCoR/HDAC3 co-repressor complex into a co-activator of AP-1- and NFκB-regulated genes. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Haydee M. Torres, Dongwook Yeo, Jennifer J. Westendorf Tags: Preview Source Type: research
Meet the authors: Lizhen Chen, Shasha Chong, and Zhijie “Jason” Liu
Here, Molecular Cell talks to first and co-corresponding author Lizhen Chen and co-corresponding authors Shasha Chong and Zhijie “Jason” Liu about their paper, ‘‘Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions’’ (in this issue of Molecular Cell) and their scientific journeys until now. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Lizhen Chen, Shasha Chong, Zhijie “Jason” Liu Tags: Q & A Source Type: research
ADAR1p150 prevents MDA5 and PKR activation via distinct mechanisms to avert fatal autoinflammation
The A-to-I RNA-editing enzyme ADAR1 has both RNA editing-dependent and -independent functions. Hu et al. report that ADAR1 prevents endogenous dsRNAs from activating both MDA5 and PKR, two innate immune sensors, through distinct mechanisms: editing dsRNAs to prevent MDA5 activation and the competitive binding of dsRNAs to inhibit PKR activation. (Source: Molecular Cell)
Source: Molecular Cell - October 4, 2023 Category: Cytology Authors: Shi-Bin Hu, Jacki Heraud-Farlow, Tao Sun, Zhen Liang, Ankita Goradia, Scott Taylor, Carl R. Walkley, Jin Billy Li Tags: Article Source Type: research
Crucial roles of the BRCA1-BARD1 E3 ubiquitin ligase activity in homology-directed DNA repair
Wang and Li et al. unveil the intricate regulatory mechanisms of BRCA1-BARD1 ubiquitylation, identify a truly ligase-null variant and another variant specifically impaired in targeting nucleosomal histones, and elucidate the pivotal roles of BRCA1-BARD1 ligase in not only early DNA end resection but also subsequ ent stages in homology-directed repair. (Source: Molecular Cell)
Source: Molecular Cell - October 4, 2023 Category: Cytology Authors: Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O ’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, A Tags: Article Source Type: research
ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei
Joo et al. uncover a surprising role for ATR in promoting rupture of micronuclei (MN). ATR phosphorylates Lamin A/C at S395 and primes S392 for CDK1 phosphorylation, destabilizing the MN envelope. ATR-driven MN rupture activates cGAS and downstream cell-autonomous and cell-non-autonomous processes, prote cting genomic integrity in cell populations. (Source: Molecular Cell)
Source: Molecular Cell - October 2, 2023 Category: Cytology Authors: Yoon Ki Joo, Elizabeth M. Black, Isabelle Trier, Wisse Haakma, Lee Zou, Lilian Kabeche Tags: Article Source Type: research
Lysosomal cyst(e)ine storage potentiates tolerance to oxidative stress in cancer cells
He et al. report that MFSD12 upregulation in breast cancer increases the lysosomal cyst(e)ine storage, providing a ready source of cyst(e)ine for GSH synthesis, which is regulated by mTORC1 to fine-tune redox homeostasis and enhance cell fitness. (Source: Molecular Cell)
Source: Molecular Cell - September 25, 2023 Category: Cytology Authors: Lixin He, Jinxin Chen, Pinwei Deng, Shumei Huang, Pian Liu, Chanjuan Wang, Xinjian Huang, Yue Li, Boyu Chen, Dongni Shi, Yunyun Xiao, Xiangfu Chen, Ying Ouyang, Libing Song, Chuyong Lin Tags: Article Source Type: research
Early fate decision for mitochondrially encoded proteins by a molecular triage
Dedicated protein quality control systems ensure the folding of newly synthesized proteins at ribosomes. Kohler et al. reveal such a system for mitochondrially encoded proteins in the form of the PHB/m-AAA protease associated with mitoribosomes. Thereby, interactions with OXPHOS assembly factors or the PHB/m-AAA protease determine the fate of nascent proteins. (Source: Molecular Cell)
Source: Molecular Cell - September 25, 2023 Category: Cytology Authors: Andreas Kohler, Andreas Carlstr öm, Hendrik Nolte, Verena Kohler, Sung-jun Jung, Sagar Sridhara, Takashi Tatsuta, Jens Berndtsson, Thomas Langer, Martin Ott Tags: Article Source Type: research
RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1 β- and RNA-dependent co-activator of osteoclast gene expression
Nuclear receptor co-repressor (NCoR) is found to maintain normal bone density by co-activating RANKL-dependent gene transcription in osteoclasts. Abe et al. resolve this paradox by demonstrating that RANKL induces RNA-dependent assembly of an NCoR/HDAC3/PGC1β complex that co-activates NF-κB and AP-1 target genes required for osteoclast differentiation. (Source: Molecular Cell)
Source: Molecular Cell - September 25, 2023 Category: Cytology Authors: Yohei Abe, Eric R. Kofman, Maria Almeida, Zhengyu Ouyang, Filipa Ponte, Jasmine R. Mueller, Grisel Cruz-Becerra, Mashito Sakai, Thomas A. Prohaska, Nathanael J. Spann, Ana Resende-Coelho, Jason S. Seidman, Joshua D. Stender, Havilah Taylor, Weiwei Fan, Ve Tags: Article Source Type: research
