A Wolf in Sheep ’s Clothing: Chromosomal Pathogenicity Islands Co-opt Phage Capsids to Facilitate Horizontal Spread
Fillol-Salom et  al. describe a mechanism by which an Escherichia coli pathogenicity island is preferentially packaged into a phage particle, thus promoting the spread of pathogenic traits among Gram-negative bacteria while protecting them from lytic infection. (Source: Molecular Cell)
Source: Molecular Cell - September 5, 2019 Category: Cytology Authors: Heather A. Feaga, Jonathan Dworkin Tags: Preview Source Type: research

N6-Methyladenosine Modification Controls Circular RNA Immunity
Mammalian cells distinguish between foreign and endogenous circular RNAs (circRNAs), but the molecular basis is unknown. Chen et  al. identify N6-methyladenosine (m6A) RNA modification as a marker for “self.” Unmodified circRNA, but not m6A-modified circRNA, activates RIG-I in the presence of K63-polyubiquitin to cause MAVS filamentation, IRF3 dimerization, and interferon production. (Source: Molecular Cell)
Source: Molecular Cell - August 29, 2019 Category: Cytology Authors: Y. Grace Chen, Robert Chen, Sadeem Ahmad, Rohit Verma, Sudhir Pai Kasturi, Laura Amaya, James P. Broughton, Jeewon Kim, Cristhian Cadena, Bali Pulendran, Sun Hur, Howard Y. Chang Tags: Article Source Type: research

Disease-Causing Mutations in SF3B1 Alter Splicing by Disrupting Interaction with SUGP1
Zhang et  al. report that SF3B1 mutations found in myelodysplastic syndromes and many cancers disrupt interaction with splicing factor SUGP1 during branchsite recognition, leading to aberrant use of upstream branch points and cryptic 3′ splice sites during RNA splicing. This defect in splicing due to canc er-causing SF3B1 mutations is rescuable. (Source: Molecular Cell)
Source: Molecular Cell - August 29, 2019 Category: Cytology Authors: Jian Zhang, Abdullah M. Ali, Yen K. Lieu, Zhaoqi Liu, Jianchao Gao, Raul Rabadan, Azra Raza, Siddhartha Mukherjee, James L. Manley Tags: Article Source Type: research

Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence
In this study, Zhang et  al. restore B cell immunity in the elderly with spermidine, a cellular polyamine metabolite depleted with age. They find that autophagy is maintained by spermidine via promoting eIF5A function and TFEB translation. This pathway provides an explanation for the age-related decline of autophagy. (Source: Molecular Cell)
Source: Molecular Cell - August 29, 2019 Category: Cytology Authors: Hanlin Zhang, Ghada Alsaleh, Jack Feltham, Yizhe Sun, Gennaro Napolitano, Thomas Riffelmacher, Philip Charles, Lisa Frau, Philip Hublitz, Zhanru Yu, Shabaz Mohammed, Andrea Ballabio, Stefan Balabanov, Jane Mellor, Anna Katharina Simon Tags: Article Source Type: research

Characterization of Fully Recombinant Human 20S and 20S-PA200 Proteasome Complexes
We report the characterization of recombinant human 20S and 20S-PA200 proteasome complexes, confirming their structural and functional integrity. In particular, the cryo-EM structure of 20S-PA200 reveals unique features, including unusual 20S proteasome conformational rearrangements, with functional consequences. (Source: Molecular Cell)
Source: Molecular Cell - August 28, 2019 Category: Cytology Authors: Ana Toste R êgo, Paula C.A. da Fonseca Tags: Article Source Type: research

Poly(ADP-Ribose) Polymerase 2 Recruits Replication Protein A to Sites of LINE-1 Integration to Facilitate Retrotransposition
Poly(ADP-ribose) polymerase 2 and the replication protein A (RPA) complex are sequentially recruited to L1 insertion sites to facilitate integration. RPA can protect single-strand L1 cDNA integration intermediates from APOBEC3-mediated cytosine deamination but also may provide a conduit to guide APOBEC3 proteins to L1 integration sites to restrict retrotransposition. (Source: Molecular Cell)
Source: Molecular Cell - August 28, 2019 Category: Cytology Authors: Tomoichiro Miyoshi, Takeshi Makino, John V. Moran Tags: Article Source Type: research

CoBATCH for High-Throughput Single-Cell Epigenomic Profiling
Wang et  al. developed a high-throughput, single-cell CoBATCH for profiling various histone modifications and DNA-binding proteins in both fixed and native conditions, uncovering epigenetic heterogeneity and inferring cell lineage diversification. (Source: Molecular Cell)
Source: Molecular Cell - August 27, 2019 Category: Cytology Authors: Qianhao Wang, Haiqing Xiong, Shanshan Ai, Xianhong Yu, Yaxi Liu, Jiejie Zhang, Aibin He Tags: Technology Source Type: research

Co-temporal Force and Fluorescence Measurements Reveal a Ribosomal Gear Shift Mechanism of Translation Regulation by Structured mRNAs
Desai et  al. used optical tweezers with single-molecule fluorescence detection to show that mRNA hairpin opening and translocation by the ribosome occur concurrently. Moreover, they unravel an allosteric gear shift mechanism of translation regulation in which ribosomes switch into an alternative, slower ki netic pathway in response to strong mRNA hairpins. (Source: Molecular Cell)
Source: Molecular Cell - August 27, 2019 Category: Cytology Authors: Varsha P. Desai, Filipp Frank, Antony Lee, Maurizio Righini, Laura Lancaster, Harry F. Noller, Ignacio Tinoco, Carlos Bustamante Tags: Article Source Type: research

Single-Nucleotide-Resolution Computing and Memory in Living Cells
Farzadfard et  al. developed a DNA writing platform that uses the genome to execute analog and digital information processing and storage in bacterial and eukaryotic cells. The platform enables recording and programming of the sequence and timing of molecular events in living cells. (Source: Molecular Cell)
Source: Molecular Cell - August 22, 2019 Category: Cytology Authors: Fahim Farzadfard, Nava Gharaei, Yasutomi Higashikuni, Giyoung Jung, Jicong Cao, Timothy K. Lu Tags: Article Source Type: research

Plasticity of the Cullin-RING Ligase Repertoire Shapes Sensitivity to Ligand-Induced Protein Degradation
Mayor-Ruiz et  al. combine functional genomics and quantitative proteomics to identify cellular modulators of ligand-induced targeted protein degradation. Several regulators, such as CAND1 and the COP9 signalosome, maintain context-specific ligase plasticity to enable substrate-driven ligase assembly and protect substrate receptors from auto-degradation. (Source: Molecular Cell)
Source: Molecular Cell - August 22, 2019 Category: Cytology Authors: Cristina Mayor-Ruiz, Martin G. Jaeger, Sophie Bauer, Matthias Brand, Celine Sin, Alexander Hanzl, Andr é C. Mueller, Jörg Menche, Georg E. Winter Tags: Short Article Source Type: research

Non-canonical mTORC2 Signaling Regulates Brown Adipocyte Lipid Catabolism through SIRT6-FoxO1
Jung et  al. identify an mTORC2-SIRT6-FoxO1 pathway in brown adipocyte that suppresses lipid catabolism and UCP1 expression independently of mTORC2’s role in promoting de novo lipogenesis. Mice lacking brown fat mTORC2 are protected against diet-induced obesity, uncovering a new mechanism in brown fat th at regulates systemic metabolic homeostasis. (Source: Molecular Cell)
Source: Molecular Cell - August 22, 2019 Category: Cytology Authors: Su Myung Jung, Chien-Min Hung, Samuel R. Hildebrand, Joan Sanchez-Gurmaches, Barbara Martinez-Pastor, Jivani M. Gengatharan, Martina Wallace, Dimpi Mukhopadhyay, Camila Martinez Calejman, Amelia K. Luciano, Wen-Yu Hsiao, Yuefeng Tang, Huawei Li, Danette L Tags: Article Source Type: research

Proximity RNA Labeling by APEX-Seq Reveals the Organization of Translation Initiation Complexes and Repressive RNA Granules
In this issue of Molecular Cell, Padr ón et al. develop an RNA proximity labeling technique that maps subcellular RNA organization comprehensively. A powerful aspect of APEX-seq is the ability to match RNA proximity labeling with spatial proteomics for a comprehensive picture of the landscape of the cell. (Source: Molecular Cell)
Source: Molecular Cell - August 22, 2019 Category: Cytology Authors: Alejandro Padr ón, Shintaro Iwasaki, Nicholas T. Ingolia Tags: Resource Source Type: research

The Gene-Silencing Protein MORC-1 Topologically Entraps DNA and Forms Multimeric Assemblies to Cause DNA Compaction
MORC proteins in plants and animals regulate the compaction of chromatin, but the molecular mechanism is unknown. Kim et  al. demonstrate that the Caenorhabditis elegans MORC-1 dimers can directly compact DNA by topologically entrapping DNA loops. Multiple MORC-1 dimers can also interact to form discrete foci of compacted DNA. (Source: Molecular Cell)
Source: Molecular Cell - August 22, 2019 Category: Cytology Authors: HyeongJun Kim, Linda Yen, Somsakul P. Wongpalee, Jessica A. Kirshner, Nicita Mehta, Yan Xue, Jonathan B. Johnston, Alma L. Burlingame, John K. Kim, Joseph J. Loparo, Steve E. Jacobsen Tags: Article Source Type: research

Toward a Comprehensive View of MicroRNA Biology
In this issue of Molecular Cell, two complementary studies illuminate miRNA biology with unprecedented depth and breadth. Reichholf et  al. (2019) present a quantitative view of miRNA biogenesis and turnover, while Becker et al. (2019) describe an exhaustive evaluation of miRNA target recognition. (Source: Molecular Cell)
Source: Molecular Cell - August 22, 2019 Category: Cytology Authors: Yao Xiao, Ian J. MacRae Tags: Preview Source Type: research

Histone Acetyltransferase 1 Links Metabolism and Transcription to Cell-Cycle Progression
HAT1 is an essential gene in mammals that acetylates newly synthesized histone H4 and is involved in chromatin assembly and genome maintenance. In this issue of Molecular Cell, Gruber et  al. (2019) show that HAT1 binds to and stimulates H4 gene expression in a growth-factor- and glucose-dependent manner. (Source: Molecular Cell)
Source: Molecular Cell - August 22, 2019 Category: Cytology Authors: John M. Denu Tags: Preview Source Type: research

Walter Neupert (1939 –2019)
The scientific community is saddened by the passing of Walter Neupert, an exceptional scientist and outstanding mentor, who contributed to shaping molecular cell biology over a career that spanned more than five decades. As a founder of the field of mitochondrial protein biogenesis, his research provided key mechanistic insights  into the fundamental process of cellular protein sorting and membrane translocation. Mitochondria have an important role in metabolism and cell regulation, and defects in their functions are a major cause of human diseases. (Source: Molecular Cell)
Source: Molecular Cell - August 22, 2019 Category: Cytology Authors: Nikolaus Pfanner, Richard Zimmermann, F. Ulrich Hartl Tags: Obituary Source Type: research

α-Ketoglutarate-Activated NF-κB Signaling Promotes Compensatory Glucose Uptake and Brain Tumor Development
Cancer cells often rewire their metabolic pathways for adaption to nutrient deficiency within tumors. Wang et  al. demonstrate here that GDH1 interacts with IKK complex and provides a local source of α-KG, which directly activates IKKβ and NF-κB signaling, thereby promoting glucose uptake, tumor cell survival, and brain tumor development. (Source: Molecular Cell)
Source: Molecular Cell - August 22, 2019 Category: Cytology Authors: Xiongjun Wang, Ruilong Liu, Xiujuan Qu, Hua Yu, Huiying Chu, Yajuan Zhang, Wencheng Zhu, Xueyuan Wu, Hong Gao, Bangbao Tao, Wenfeng Li, Ji Liang, Guohui Li, Weiwei Yang Tags: Article Source Type: research

SLX4IP Antagonizes Promiscuous BLM Activity during ALT Maintenance
Panier et  al. reveal that SLX4IP is a regulator of ALT telomere maintenance that binds to both BLM and SLX4 and influences the balance between resolution and dissolution at recombining telomeres. Its importance for the ALT process is underscored by the finding that SLX4IP is inactivated in a subset of ALT-p ositive osteosarcomas. (Source: Molecular Cell)
Source: Molecular Cell - August 22, 2019 Category: Cytology Authors: Stephanie Panier, Marija Maric, Graeme Hewitt, Emily Mason-Osann, Himabindu Gali, Anqi Dai, Adam Labadorf, Jean-Hugues Guervilly, Philip Ruis, Sandra Segura-Bayona, Ondrej Belan, Paulina Marzec, Pierre-Henri L. Gaillard, Rachel L. Flynn, Simon J. Boulton Tags: Article Source Type: research

Regulation of Co-transcriptional Pre-mRNA Splicing by m6A through the Low-Complexity Protein hnRNPG
Zhou et  al. show that the m6A reader protein hnRNPG interacts with m6A-modified nascent pre-mRNA and the phosphorylated C-terminal domain of RNA polymerase II to regulate alternative splicing. These interactions depend on an RGG region in the low-complexity region of hnRNPG. (Source: Molecular Cell)
Source: Molecular Cell - August 21, 2019 Category: Cytology Authors: Katherine I. Zhou, Hailing Shi, Ruitu Lyu, Adam C. Wylder, Żaneta Matuszek, Jessica N. Pan, Chuan He, Marc Parisien, Tao Pan Tags: Article Source Type: research

Msp1 Clears Mistargeted Proteins by Facilitating Their Transfer from Mitochondria to the ER
Msp1 extracts mistargeted tail-anchored (TA) proteins from the mitochondrial outer membrane for reinsertion into the ER membrane. The ER-membrane-inserted TA proteins are then subjected to the ER quality control system, i.e., ubiquitination by Doa10 and subsequent re-extraction by Cdc48 to the cytosol for proteasomal degradation. (Source: Molecular Cell)
Source: Molecular Cell - August 21, 2019 Category: Cytology Authors: Shunsuke Matsumoto, Kunio Nakatsukasa, Chika Kakuta, Yasushi Tamura, Masatoshi Esaki, Toshiya Endo Tags: Article Source Type: research

Evolution of Inosine-Specific Endonuclease V from Bacterial DNase to Eukaryotic RNase
Wu et  al. show that bacterial Endonuclease V (EndoV) cleaves DNA in the presence of an inosine (deaminated adenosine), but eukaryotic EndoV, due to insertions in two non-conserved loops, cleaves inosine-containing RNA only. A similar DNA-to-RNA evolution also occurs in Argonaute. (Source: Molecular Cell)
Source: Molecular Cell - August 20, 2019 Category: Cytology Authors: Jinjun Wu, Nadine L. Samara, Isao Kuraoka, Wei Yang Tags: Article Source Type: research

Proteomics Links Ubiquitin Chain Topology Change to Transcription Factor Activation
Li et  al. discovered that a chain topology change from K48 to K11 linkages on the transcription factor Met4 reduces competition between the K48 chain and the basal transcription complex for binding to the Met4 tandem UBD. These findings provided insight into the role of ubiquitin chain topologies in ubi quitin signaling. (Source: Molecular Cell)
Source: Molecular Cell - August 20, 2019 Category: Cytology Authors: Yanchang Li, Eric B. Dammer, Yuan Gao, Qiuyan Lan, Mark A. Villamil, Duc M. Duong, Chengpu Zhang, Lingyan Ping, Linda Lauinger, Karin Flick, Zhongwei Xu, Wei Wei, Xiaohua Xing, Lei Chang, Jianping Jin, Xuechuan Hong, Yunping Zhu, Junzhu Wu, Zixin Deng, Fu Tags: Article Source Type: research

Conserved Pseudoknots in lncRNA MEG3 Are Essential for Stimulation of the p53 Pathway
Uroda et  al. identify the structural and functional core of the human lncRNA MEG3, revealing that point mutations designed to disrupt the MEG3 fold impair function. The work proves the importance of lncRNA tertiary structure motifs for selective and specific control of key cellular processes such as the p5 3 stress response. (Source: Molecular Cell)
Source: Molecular Cell - August 20, 2019 Category: Cytology Authors: Tina Uroda, Eleni Anastasakou, Annalisa Rossi, Jean-Marie Teulon, Jean-Luc Pellequer, Paolo Annibale, Ombeline Pessey, Alberto Inga, Isabel Chill ón, Marco Marcia Tags: Article Source Type: research

Dynamic Enhancer DNA Methylation as Basis for Transcriptional and Cellular Heterogeneity of ESCs
Song et  al. used an allelic reporter approach to show super-enhancers allelic DNA methylation dynamics underlies locus-specific heterogeneity, which functionally impacts transcription and cellular states of mouse embryonic stem cells. (Source: Molecular Cell)
Source: Molecular Cell - August 15, 2019 Category: Cytology Authors: Yuelin Song, Patrick R. van den Berg, Styliani Markoulaki, Frank Soldner, Alessandra Dall ’Agnese, Jonathan E. Henninger, Jesse Drotar, Nicholas Rosenau, Malkiel A. Cohen, Richard A. Young, Stefan Semrau, Yonatan Stelzer, Rudolf Jaenisch Tags: Article Source Type: research

Naa10p Inhibits Beige Adipocyte-Mediated Thermogenesis through N- α-acetylation of Pgc1α
Lee et  al. reveal that Naa10p-mediated N-terminal acetylation of Pgc1α inhibits beige thermogenesis and promotes diet-induced obesity (DIO) in mice. Together with the fact that NAA10 expression positively correlates with human obesity, their results suggest that inhibiting the enzymatic activity of Naa1 0p in adipose tissues may suppress DIO. (Source: Molecular Cell)
Source: Molecular Cell - August 15, 2019 Category: Cytology Authors: Chen-Cheng Lee, Yi-Chun Shih, Ming-Lun Kang, Yi-Cheng Chang, Lee-Ming Chuang, Ramanan Devaraj, Li-Jung Juan Tags: Article Source Type: research

Transcriptional Bursting and Co-bursting Regulation by Steroid Hormone Release Pattern and Transcription Factor Mobility
Stavreva et  al. reveal a delay between glucocorticoid receptor (GR) binding and RNA synthesis and link GR mobility modulations in time- and treatment-dependent manner to the size and frequency of transcriptional bursts based on single molecule experiments. By reconstructing GR signaling dynamics on timescales ranging from days to milliseconds, they relate single-cell and single-molecule phenomena to glucocorticoid physiology. (Source: Molecular Cell)
Source: Molecular Cell - August 14, 2019 Category: Cytology Authors: Diana A. Stavreva, David A. Garcia, Gregory Fettweis, Prabhakar R. Gudla, George F. Zaki, Vikas Soni, Andrew McGowan, Geneva Williams, Anh Huynh, Murali Palangat, R. Louis Schiltz, Thomas A. Johnson, Diego M. Presman, Matthew L. Ferguson, Gianluca Pegorar Tags: Article Source Type: research

Nucleo-cytoplasmic Partitioning of ARF Proteins Controls Auxin Responses in Arabidopsis thaliana
ARF transcription factors mediate the activity of the phytohormone auxin, regulating every aspect of plant development. Powers et  al. determine that some ARFs undergo phase transition to form large-order cytoplasmic protein assemblies that limit auxin responsiveness in a developmentally relevant context, illustrating a strong link between condensate formation and biological function. (Source: Molecular Cell)
Source: Molecular Cell - August 14, 2019 Category: Cytology Authors: Samantha K. Powers, Alex S. Holehouse, David A. Korasick, Katherine H. Schreiber, Natalie M. Clark, Hongwei Jing, Ryan Emenecker, Soeun Han, Eric Tycksen, Ildoo Hwang, Rosangela Sozzani, Joseph M. Jez, Rohit V. Pappu, Lucia C. Strader Tags: Article Source Type: research

One-Carbon Metabolism Supports S-Adenosylmethionine and Histone Methylation to Drive Inflammatory Macrophages
The biochemical underpinnings of immune cells affect their function and influence host immunity. Yu and colleagues demonstrate that LPS stimulates the PPP, SSP, and one-carbon metabolism, the synergism of which drives epigenetic reprogramming for LPS-induced inflammation. (Source: Molecular Cell)
Source: Molecular Cell - August 13, 2019 Category: Cytology Authors: Weiwei Yu, Zhen Wang, Kailian Zhang, Zhexu Chi, Ting Xu, Danlu Jiang, Sheng Chen, Wenxin Li, Xuyan Yang, Xue Zhang, Yingliang Wu, Di Wang Tags: Article Source Type: research

Estrogen-Related Hormones Induce Apoptosis by Stabilizing Schlafen-12 Protein Turnover
Estrogen-like female sex hormones at concentrations present in human placenta induce apoptosis. They do so by binding to phosphodiesterase 3A, which in turn recruits and stabilizes Schlafen 12 protein, whose elevated level stops the protein translation on ER, resulting in downregulation of anti-apoptotic proteins Bcl-2 and Mcl-1 and subsequent apoptosis. (Source: Molecular Cell)
Source: Molecular Cell - August 13, 2019 Category: Cytology Authors: Dianrong Li, Jie Chen, Youwei Ai, Xiaoqiong Gu, Li Li, Di Che, Zhaodi Jiang, Lin Li, She Chen, Huangwei Huang, Jiawen Wang, Tao Cai, Yang Cao, Xiangbin Qi, Xiaodong Wang Tags: Article Source Type: research

Mutation Rate Heterogeneity Increases Odds of Survival in Unpredictable Environments
Matic reviews the evidence that the heterogeneity of mutation rates is very common in bacterial populations. Such heterogeneity, which can result from genetic, environmental, and stochastic effects, may increase the rate of complex adaptation without reducing the mean fitness of a population. (Source: Molecular Cell)
Source: Molecular Cell - August 8, 2019 Category: Cytology Authors: Ivan Matic Tags: Perspective Source Type: research

Reaction Mechanisms of Pol IV, RDR2, and DCL3 Drive RNA Channeling in the siRNA-Directed DNA Methylation Pathway
siRNA-directed DNA methylation is important for genome defense against transposons and viruses. Singh et  al. recapitulate siRNA biogenesis in vitro using NUCLEAR RNA POLYMERASE IV, RNA-DEPENDENT RNA POLYMERASE 2, and DICER-LIKE 3, providing mechanistic insights into Pol IV termination, RDR2 activation, siRNA precursor strand specification, and DCL3 dicing. (Source: Molecular Cell)
Source: Molecular Cell - August 8, 2019 Category: Cytology Authors: Jasleen Singh, Vibhor Mishra, Feng Wang, Hsiao-Yun Huang, Craig S. Pikaard Tags: Article Source Type: research

Enhancer Features that Drive Formation of Transcriptional Condensates
Shrinivas et  al. demonstrate that specific types of motif compositions encoded in DNA drive localized formation of transcriptional condensates. These findings explain how phase separation can occur at specific genomic locations and shed light on why only some genomic loci become highly active enhancers. (Source: Molecular Cell)
Source: Molecular Cell - August 8, 2019 Category: Cytology Authors: Krishna Shrinivas, Benjamin R. Sabari, Eliot L. Coffey, Isaac A. Klein, Ann Boija, Alicia V. Zamudio, Jurian Schuijers, Nancy M. Hannett, Phillip A. Sharp, Richard A. Young, Arup K. Chakraborty Tags: Article Source Type: research

REV1-POL ζ Inhibition and Cancer Therapy
In a recent issue of Cell, Wojtaszek et  al. (2019) reported a small-molecule inhibitor of mutagenic translesion DNA synthesis, which targets the interaction between REV1 and REV7, sensitizes cancer cells to cisplatin in vitro and in vivo, and reduces mutagenesis. (Source: Molecular Cell)
Source: Molecular Cell - August 8, 2019 Category: Cytology Authors: Toshiyasu Taniguchi Tags: Spotlight Source Type: research

Manipulation by Methylation: Garnishing mRNAs with m6Am
In two recent publications in Molecular Cell, Boulias et  al. (2019) and Sendinc et al. (2019) use complementary approaches to map m6Am modification sites transcriptome-wide and demonstrate that m6Am can repress translation while increasing the stability of a subset of low-abundance transcripts. (Source: Molecular Cell)
Source: Molecular Cell - August 8, 2019 Category: Cytology Authors: Katelyn A. Doxtader, Yunsun Nam Tags: Preview Source Type: research

Quality Control in the ER: Misfolded Prohormones Get a Checkup
In Mutant INS-gene-induced Diabetes of Youth (MIDY) syndrome, mutant proinsulin aggregates interfere with the folding of wild-type proinsulin in the endoplasmic reticulum, ultimately decreasing insulin secretion. In this issue of Molecular Cell, Cunningham et  al. (2019) identify two mechanisms by which prohormone aggregation is prevented and cleared. (Source: Molecular Cell)
Source: Molecular Cell - August 8, 2019 Category: Cytology Authors: Macy L. Sprunger, Meredith E. Jackrel Tags: Preview Source Type: research

Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis
This work illustrates the heterogeneity of liver non-parenchymal cells (NPCs) and their reprogramming during NASH pathogenesis. Using single-cell RNA-sequencing analysis, the authors mapped the landscape of the intrahepatic ligand-receptor signaling network and revealed two fundamental aspects of HSC biology: stellakine secretion and contractile response to vasoactive hormones. Hepatic vascular dysfunction and emergence of Trem2+ NASH-associated macrophages (NAMs) are two conserved features of mouse and human NASH. (Source: Molecular Cell)
Source: Molecular Cell - August 8, 2019 Category: Cytology Authors: Xuelian Xiong, Henry Kuang, Sahar Ansari, Tongyu Liu, Jianke Gong, Shuai Wang, Xu-Yun Zhao, Yewei Ji, Chuan Li, Liang Guo, Linkang Zhou, Zhimin Chen, Paola Leon-Mimila, Meng Ting Chung, Katsuo Kurabayashi, Judy Opp, Francisco Campos-P érez, Hugo Villamil Tags: Resource Source Type: research

Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P2 Synthesis
Nishimura et  al. show that the Osh lipid exchange proteins are required for PI(4,5)P2 synthesis, a key regulator of global plasma membrane organization and function. The Osh proteins form a unique membrane lipid environment with unsaturated phosphatidylserine and sterols that specifies PIP 5-kinase activity at the plasma membrane. (Source: Molecular Cell)
Source: Molecular Cell - August 8, 2019 Category: Cytology Authors: Taki Nishimura, Michael Gecht, Roberto Covino, Gerhard Hummer, Michal A. Surma, Christian Klose, Hiroyuki Arai, Nozomu Kono, Christopher J. Stefan Tags: Article Source Type: research

Bicoid-Dependent Activation of the Target Gene hunchback Requires a Two-Motif Sequence Code in a Specific Basal Promoter
Ling et  al. identify a two-motif sequence code that is required and sufficient for activation of a specific promoter by the transcription factor Bicoid. They suggest that binding a single factor to both enhancers and promoters increases the probability that they will interact. (Source: Molecular Cell)
Source: Molecular Cell - August 8, 2019 Category: Cytology Authors: Jia Ling, Kristaley Yui Umezawa, Theresa Scott, Stephen Small Tags: Article Source Type: research

Nascent Polypeptide Domain Topology and Elongation Rate Direct the Cotranslational Hierarchy of Hsp70 and TRiC/CCT
Stein et  al. demonstrate that chaperones Hsp70/Ssb and TRiC/CCT— essential for maintaining proteostasis—sequentially associate with nascent polypeptides, and they uncover the principles driving this hierarchical recognition. They show that Hsp70 and TRiC recognize specific and distinct topological prop erties in ribosome-bound nascent folding intermediates, acting in coordination with translation elongation slowdowns. (Source: Molecular Cell)
Source: Molecular Cell - August 7, 2019 Category: Cytology Authors: Kevin C. Stein, Allison Kriel, Judith Frydman Tags: Article Source Type: research

RAD51AP1 Is an Essential Mediator of Alternative Lengthening of Telomeres
Barroso-Gonz ález et al. identify that disruption of the HR accessory factor RAD51AP1 disrupts ALT telomere elongation, causing telomere damage and fragmentation. Rather than dying, these cancer cells activate autophagy as a survival mechanism. The importance of RAD51AP1 in ALT cancer cells is underscored by i ts specific stabilization by SUMOylated mediated mechanisms. (Source: Molecular Cell)
Source: Molecular Cell - August 7, 2019 Category: Cytology Authors: Jonathan Barroso-Gonz ález, Laura García-Expósito, Song My Hoang, Michelle L. Lynskey, Justin L. Roncaioli, Arundhati Ghosh, Callen T. Wallace, Mauro Modesti, Kara A. Bernstein, Saumendra N. Sarkar, Simon C. Watkins, Roderick J. O’Sullivan Tags: Article Source Type: research

RNA 5-Methylcytosine Facilitates the Maternal-to-Zygotic Transition by Preventing Maternal mRNA Decay
RNA modifications exert important effects in many critical physiological processes. Using RNA-BisSeq, Yang et  al. provide a comprehensive view of the RNA m5C landscape in zebrafish early embryos and show that m5C-modified maternal mRNAs are stabilized by Ybx1 and Pabpc1a during zebrafish MZT. (Source: Molecular Cell)
Source: Molecular Cell - August 6, 2019 Category: Cytology Authors: Ying Yang, Lu Wang, Xiao Han, Wen-Lan Yang, Mengmeng Zhang, Hai-Li Ma, Bao-Fa Sun, Ang Li, Jun Xia, Jing Chen, Jian Heng, Baixing Wu, Yu-Sheng Chen, Jia-Wei Xu, Xin Yang, Huan Yao, Jiawei Sun, Cong Lyu, Hai-Lin Wang, Ying Huang, Ying-Pu Sun, Yong-Liang Zh Tags: Article Source Type: research

The Histone Deacetylase SIRT6 Restrains Transcription Elongation via Promoter-Proximal Pausing
Historically, histone deacetylases have been described as inhibitors of transcription initiation by compacting chromatin at the transcriptional starting site. Etchegaray et  al. identified the histone deacetylase SIRT6 as a critical modulator of transcriptional pausing and elongation, acting downstream of recruitment of Pol II. (Source: Molecular Cell)
Source: Molecular Cell - August 6, 2019 Category: Cytology Authors: Jean-Pierre Etchegaray, Lei Zhong, Catherine Li, Telmo Henriques, Eileen Ablondi, Tomoyoshi Nakadai, Capucine Van Rechem, Christina Ferrer, Kenneth N. Ross, Jee-Eun Choi, Ann Samarakkody, Fei Ji, Andrew Chang, Ruslan I. Sadreyev, Sridhar Ramaswamy, Sergei Tags: Article Source Type: research

MISTERMINATE Mechanistically Links Mitochondrial Dysfunction with Proteostasis Failure
Non-templated C-terminal alanine (Ala) and threonine (Thr) addition to nascent peptides occurs during translational stalling. So far, this CAT-tailing phenomenon has only been shown with reporter constructs. Wu et  al. describe a CAT-tailing-like MISTERMINATE process happening to respiratory chain proteins in Parkinson’s disease models and patient cells, linking CAT-tailing to neurodegenerative disease. (Source: Molecular Cell)
Source: Molecular Cell - August 1, 2019 Category: Cytology Authors: Zhihao Wu, Ishaq Tantray, Junghyun Lim, Songjie Chen, Yu Li, Zoe Davis, Cole Sitron, Jason Dong, Suzana Gispert, Georg Auburger, Onn Brandman, Xiaolin Bi, Michael Snyder, Bingwei Lu Tags: Article Source Type: research

Thermophile 90S Pre-ribosome Structures Reveal the Reverse Order of Co-transcriptional 18S rRNA Subdomain Integration
Cheng et  al. report a series of 90S pre-ribosome structures that reveal a reverse order of 18S rRNA subdomain incorporation. Accordingly, the 5′ domain is stably assembled only after the 3′ and central domains have been integrated into the 90S. This final compaction depends on the conserved Kre33-Enp2- Bfr2-Lcp5 module. (Source: Molecular Cell)
Source: Molecular Cell - August 1, 2019 Category: Cytology Authors: Jingdong Cheng, Jochen Ba ßler, Paulina Fischer, Benjamin Lau, Nikola Kellner, Ruth Kunze, Sabine Griesel, Martina Kallas, Otto Berninghausen, Daniela Strauss, Roland Beckmann, Ed Hurt Tags: Article Source Type: research

The Magnitude of IFN- γ Responses Is Fine-Tuned by DNA Architecture and the Non-coding Transcript of Ifng-as1
Petermann et  al. report that the long non-coding RNA locus Ifng-as1 is an important regulator of Ifng. It does so through its role as a modifier of DNA structure, but also through transcription of the lncRNA itself, which is involved in dynamic and cell state-specific regulation of IFN-γ-mediated host defense . (Source: Molecular Cell)
Source: Molecular Cell - July 31, 2019 Category: Cytology Authors: Franziska Petermann, Aleksandra P ękowska, Catrina A. Johnson, Dragana Jankovic, Han-Yu Shih, Kan Jiang, William H. Hudson, Stephen R. Brooks, Hong-Wei Sun, Alejandro V. Villarino, Chen Yao, Kentner Singleton, Rama S. Akondy, Yuka Kanno, Alan Sher, Rafae Tags: Article Source Type: research

Early Scanning of Nascent Polypeptides inside the Ribosomal Tunnel by NAC
NAC is an essential ribosome-associated protein biogenesis factor. Gamerdinger et  al. demonstrate that NAC deeply inserts into the ribosomal tunnel to sense nascent polypeptide chains directly upon birth. The early scanning of nascent polypeptides inside the ribosomal tunnel is crucial for the correct sorting of proteins in the cell. (Source: Molecular Cell)
Source: Molecular Cell - July 31, 2019 Category: Cytology Authors: Martin Gamerdinger, Kan Kobayashi, Annalena Wallisch, Stefan G. Kreft, Carolin Sailer, Renate Schl ömer, Nadine Sachs, Ahmad Jomaa, Florian Stengel, Nenad Ban, Elke Deuerling Tags: Article Source Type: research

Heterozygous Mutations in SMARCA2 Reprogram the Enhancer Landscape by Global Retargeting of SMARCA4
Mutations in subunits of the SWI/SNF complex cause developmental disorders associated with intellectual disability and speech delay. However, the mechanistic basis of disease is poorly understood. Gao et  al. show that disease-associated SMARCA2 mutations lead to impaired neural differentiation due to changes in transcription factor expression that drive enhancer reprogramming. (Source: Molecular Cell)
Source: Molecular Cell - July 30, 2019 Category: Cytology Authors: Fangjian Gao, Nicholas J. Elliott, Josephine Ho, Alexzander Sharp, Maxim N. Shokhirev, Diana C. Hargreaves Tags: Article Source Type: research

The N-Degron Pathway Mediates ER-phagy
Ji et  al. show that the N-degron pathway mediates ER-phagy for ER protein quality control, initiated by the interaction of the autophagic cargo adaptor p62 and the transmembrane E3 ligase TRIM13. Ubiquitination of TRIM13 and the N-terminal arginine residue of N-degron substrates such as BiP/GRP78 functi on as ER-phagy degrons. (Source: Molecular Cell)
Source: Molecular Cell - July 30, 2019 Category: Cytology Authors: Chang Hoon Ji, Hee Yeon Kim, Ah Jung Heo, Su Hyun Lee, Min Ju Lee, Su Bin Kim, Ganipisetti Srinivasrao, Su Ran Mun, Hyunjoo Cha-Molstad, Aaron Ciechanover, Cheol Yong Choi, Hee Gu Lee, Bo Yeon Kim, Yong Tae Kwon Tags: Article Source Type: research

Transcription Restart Establishes Chromatin Accessibility after DNA Replication
(Molecular Cell 75, 284 –297.e1–e6; July 25, 2019) (Source: Molecular Cell)
Source: Molecular Cell - July 25, 2019 Category: Cytology Authors: Kathleen R. Stewart-Morgan, Nazaret Rever ón-Gómez, Anja Groth Tags: Correction Source Type: research

Compartments in the Ring
Sister chromatid cohesion has been thought to be mediated by DNA entrapment within the large cohesin ring. Vazquez Nunez et  al. and Chapard et al. now show that the ring is divided up into two sub-compartments, with implications for how these chromosomal organizers entrap DNA. (Source: Molecular Cell)
Source: Molecular Cell - July 25, 2019 Category: Cytology Authors: Tomoko Nishiyama Tags: Preview Source Type: research