Cell Reports
All content is freely available to readers and supported through open access

Mar 22, 2022

Volume 38Issue 12
Open Access
On the cover: Ebola RNA polymerase must navigate cellular defense mechanisms, while hijacking host factors to drive replication of the viral genome. Fang et al. used proximity proteomics to decipher functional connections between Ebola polymerase and host cellular proteins. The resulting interactome reveals a dynamic interplay between cellular RNA decay factors and viral replication. The cover art symbolizes pathways to Ebola viral polymerase and attraction of other factors in the complex cellular environment. Image by Jingru Fang....
On the cover: Ebola RNA polymerase must navigate cellular defense mechanisms, while hijacking host factors to drive replication of the viral genome. Fang et al. used proximity proteomics to decipher functional connections between Ebola polymerase and host cellular proteins. The resulting interactome reveals a dynamic interplay between cellular RNA decay factors and viral replication. The cover art symbolizes pathways to Ebola viral polymerase and attraction of other factors in the complex cellular environment. Image by Jingru Fang.


  • Neddylation is essential for β-catenin degradation in Wnt signaling pathway

    • Bojun Wang,
    • Tiantian Wang,
    • Huimin Zhu,
    • Rong Yan,
    • Xinru Li,
    • Chengqian Zhang,
    • Wanyu Tao,
    • Xisong Ke,
    • Piliang Hao,
    • Yi Qu
    Wang et al. report a central role of neddylation for β-catenin degradation in Wnt signaling. They also identify β-TrCP2 as a candidate E3 ligase for β-catenin neddylation and demonstrate that GSK3 and APC are not required for β-catenin neddylation but essential for the subsequent degradation.


  • Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation

    • Anand P. Singh,
    • Ping Wu,
    • Sergey Ryabichko,
    • João Raimundo,
    • Michael Swan,
    • Eric Wieschaus,
    • Thomas Gregor,
    • Jared E. Toettcher
    Singh et al. investigate how rapid changes in nuclear Bicoid levels dynamically regulate expression of its target genes. Combining optogenetic stimulation and a simplified genetic background, their results recapitulate the canonical role of Bicoid as a transcriptional activator and reveal a possible noncanonical role in direct kni repression.
  • ZFP541 maintains the repression of pre-pachytene transcriptional programs and promotes male meiosis progression

    • Jianze Xu,
    • Jianing Gao,
    • Junyan Liu,
    • Xue Huang,
    • Huan Zhang,
    • Ao Ma,
    • Jingwei Ye,
    • Xingxia Zhang,
    • Yang Li,
    • Gang Yang,
    • Hao Yin,
    • Ranjha Khan,
    • Tao Li,
    • Suixing Fan,
    • Xiaohua Jiang,
    • Yuanwei Zhang,
    • Hanwei Jiang,
    • Hui Ma,
    • Qinghua Shi
    Xu et al. demonstrate that ZFP541 predominantly maintains the repression of pre-pachytene transcriptional programs, including meiotic DSB formation genes, in pachytene spermatocytes and suppresses aberrant DSB formation after mid-pachytene, thus ensuring meiosis progression.
  • SPT16 ubiquitylation by DCAF14-CRL4 regulates FACT binding to histones

    • Tadashi Nakagawa,
    • Akane Morohoshi,
    • Yuko Nagasawa,
    • Makiko Nakagawa,
    • Masaki Hosogane,
    • Yasuhiro Noda,
    • Toru Hosoi,
    • Keiko Nakayama
    The histone chaperone FACT plays a role in DNA replication, transcription, and repair, but its regulation is unclear. Nakagawa et al. report that DCAF14-CRL4 ubiquitylates the FACT subunit SPT16 and that such ubiquitylation may regulate DNA replication-coupled histone incorporation into chromatin and thereby ensure efficient S-phase progression.
  • Mobile origin-licensing factors confer resistance to conflicts with RNA polymerase

    • Matthias J. Scherr,
    • Syafiq Abd Wahab,
    • Dirk Remus,
    • Karl E. Duderstadt
    Scherr et al. report a single-molecule imaging approach that provides a real-time view of encounters between RNA polymerase and replication origin-licensing factors. They show that origin-licensing factors can be pushed to new locations by RNA polymerase to support alternative origin specification pathways.
  • BMI-1 regulates DNA end resection and homologous recombination repair

    • Amira Fitieh,
    • Andrew J. Locke,
    • Fatemeh Mashayekhi,
    • Fajr Khaliqdina,
    • Ajit K. Sharma,
    • Ismail Hassan Ismail
    Fitieh et al. report the Polycomb group protein BMI-1 promotes homologous recombination (HR) repair of DNA double-strand break lesions. BMI-1 promotes DNA end resection, an event preceding HR, by inhibiting RNA-polymerase-II-dependent transcription, and by facilitating deposition of the H2AK119ub chromatin mark, which helps recruit the resection factor CtIP.
  • Cdc48 influence on separase levels is independent of mitosis and suggests translational sensitivity of separase

    • Drisya Vijayakumari,
    • Janina Müller,
    • Silke Hauf
    Vijayakumari et al. provide evidence against the long-standing hypothesis that low levels of separase in the S. pombe cdc48-353 mutant are caused by mitotic co-degradation of separase, along with its binding partner securin. Instead, separase protein synthesis may be defective in cdc48-353 cells.
  • A 3D transcriptomics atlas of the mouse nose sheds light on the anatomical logic of smell

    • Mayra L. Ruiz Tejada Segura,
    • Eman Abou Moussa,
    • Elisa Garabello,
    • Thiago S. Nakahara,
    • Melanie Makhlouf,
    • Lisa S. Mathew,
    • Li Wang,
    • Filippo Valle,
    • Susie S.Y. Huang,
    • Joel D. Mainland,
    • Michele Caselle,
    • Matteo Osella,
    • Stephan Lorenz,
    • Johannes Reisert,
    • Darren W. Logan,
    • Bettina Malnic,
    • Antonio Scialdone,
    • Luis R. Saraiva
    Ruiz Tejada Segura et al. employ a spatial transcriptomics approach to create a 3D map of gene expression of the mouse nose and combine it with single-cell RNA-seq, machine learning, and chemoinformatics to resolve its molecular architecture and shed light into the anatomical logic of smell.
  • ADRAM is an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3

    • Wei Wei,
    • Qiongyi Zhao,
    • Ziqi Wang,
    • Wei-Siang Liau,
    • Dean Basic,
    • Haobin Ren,
    • Paul R. Marshall,
    • Esmi L. Zajaczkowski,
    • Laura J. Leighton,
    • Sachithrani U. Madugalle,
    • Mason Musgrove,
    • Ambika Periyakaruppiah,
    • Jichun Shi,
    • Jianjian Zhang,
    • John S. Mattick,
    • Timothy R. Mercer,
    • Robert C. Spitale,
    • Xiang Li,
    • Timothy W. Bredy
    Wei et al. use targeted RNA capture sequencing to examine experience-dependent long noncoding RNA activity in the infralimbic prefrontal cortex of adult mice. They discover a gene, which they call ADRAM, that is directly involved in the epigenomic regulation of gene expression underlying memory formation.
  • Golgin Imh1 and GARP complex cooperate to restore the impaired SNARE recycling transport induced by ER stress

    • Yi-Hsun Wang,
    • Wan-Yun Chiu,
    • Yan-Ting Chen,
    • Pei-Juan Cai,
    • Yu-Chieh Wu,
    • Jia-Lu Wu,
    • Bo-Han Chen,
    • Ya-Wen Liu,
    • Chia-Jung Yu,
    • Fang-Jen S. Lee
    Wang et al. present the cooperative action of two different classes of tethers, golgin Imh1 and GARP complex, in mediating proper recycling of SNAREs Snc1/Tlg1 under ER stress. They show that ER stress induces an Ire1-independent response mechanism, which involves the MAP kinase Slt2/ERK2-dependent Imh1 phosphorylation to maintain Snc1/Tlg1 transport.
  • Unique molecular features and cellular responses differentiate two populations of motor cortical layer 5b neurons in a preclinical model of ALS

    • Maria V. Moya,
    • Rachel D. Kim,
    • Meghana N. Rao,
    • Bianca A. Cotto,
    • Sarah B. Pickett,
    • Caroline E. Sferrazza,
    • Nathaniel Heintz,
    • Eric F. Schmidt
    Moya et al. use bacTRAP mouse lines to characterize two highly related subpopulations of layer 5b projection neurons in motor cortex that are differentially susceptible to neurodegeneration in the SOD1-G93A mouse model of ALS. They identify the regulation of genes involved in bioenergetics as a key factor regulating susceptibility.
  • Top-down feedback enables flexible coding strategies in the olfactory cortex

    • Zhen Chen,
    • Krishnan Padmanabhan
    Chen and Padmanabhan show that centrifugal feedback in the early olfactory system shapes the temporal structure of neural activity in the olfactory cortex. This allows flexible coding strategies by which to represent odor information in the olfactory cortex that improving behavioral performance in odor discrimination tasks.
  • Procr functions as a signaling receptor and is essential for the maintenance and self-renewal of mammary stem cells

    • Chunye Liu,
    • Changdong Lin,
    • Daisong Wang,
    • Jingqiang Wang,
    • Yu Tao,
    • Yue Li,
    • Xinyi Chen,
    • Lanyue Bai,
    • Yingying Jia,
    • Jianfeng Chen,
    • Yi Arial Zeng
    Liu et al. demonstrate the essential role of Procr as a signaling receptor for the maintenance and self-renewal of mammary stem cells and reveal a protein C-Procr-Hsp90-Src-IGF1R signaling axis.
  • The mTOR chromatin-bound interactome in prostate cancer

    • Catherine R. Dufour,
    • Charlotte Scholtes,
    • Ming Yan,
    • Yonghong Chen,
    • Lingwei Han,
    • Ting Li,
    • Hui Xia,
    • Qiyun Deng,
    • Mathieu Vernier,
    • Vincent Giguère
    Increasing evidence supports a direct role of nuclear mTOR in gene regulation, yet the mTOR transcriptional coregulator networks are poorly understood. Dufour et al. report an in-depth proteomics profiling of chromatin-bound mTOR interactors in AR-dependent and -independent prostate cancer models, identifying key regulators of nuclear transport, chromatin state, and transcription.
  • Prospectively defined patterns of APOBEC3A mutagenesis are prevalent in human cancers

    • Rachel A. DeWeerd,
    • Eszter Németh,
    • Ádám Póti,
    • Nataliya Petryk,
    • Chun-Long Chen,
    • Olivier Hyrien,
    • Dávid Szüts,
    • Abby M. Green
    APOBEC3 cytidine deaminases are putative cancer mutagens. DeWeerd et al. experimentally define the genome-wide spectrum of mutagenesis caused by APOBEC3A deamination activity, which includes base substitutions, deletions, and mutations of 5-methylcytidines at CpG motifs. This mutational signature is prevalent in human cancers and provides a biomarker for APOBEC3A activity.
  • Placental colonization by Fusobacterium nucleatum is mediated by binding of the Fap2 lectin to placentally displayed Gal-GalNAc

    • Lishay Parhi,
    • Jawad Abed,
    • Amjad Shhadeh,
    • Tamar Alon-Maimon,
    • Shiran Udi,
    • Shani Leviatan Ben-Arye,
    • Joseph Tam,
    • Oren Parnas,
    • Vered Padler-Karavani,
    • Debra Goldman-Wohl,
    • Simcha Yagel,
    • Ofer Mandelboim,
    • Gilad Bachrach
    Parhi et al. find that the oncofetal antigen Gal-GalNAc is displayed on trophoblast cells facing maternal blood and that its level rises during gestation. Gal-GalNAc is recognized by the Fusobacterium nucleatum lectin Fap2, facilitating fusobacterial colonization of the placenta.
  • Coupling between DNA replication, segregation, and the onset of constriction in Escherichia coli

    • Sriram Tiruvadi-Krishnan,
    • Jaana Männik,
    • Prathitha Kar,
    • Jie Lin,
    • Ariel Amir,
    • Jaan Männik
    Using high-throughput microscopy, Tiruvadi-Krishnan et al. determine timings for critical cell-cycle checkpoints related to division and replication in Escherichia coli. The data, combined with cell-cycle modeling, show that the onset of constriction is blocked by the mid-cell nucleoid. In slow-growth conditions, the blockage is limiting for cell division.
  • Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa

    • Caroline Stienne,
    • Richard Virgen-Slane,
    • Lisa Elmén,
    • Marisol Veny,
    • Sarah Huang,
    • Jennifer Nguyen,
    • Elizabeth Chappell,
    • Mary Olivia Balmert,
    • Jr-Wen Shui,
    • Michelle A. Hurchla,
    • Mitchell Kronenberg,
    • Scott N. Peterson,
    • Kenneth M. Murphy,
    • Carl F. Ware,
    • John R. Šedý
    Stienne et al. investigate how BTLA and HVEM receptors control inflammatory and metabolic signaling in lymphocytes. A major function of these receptors in intestinal lymphoid tissue is to regulate mucosal antibody production. Ultimately, this system controls the composition of the intestinal microbiome, including pathogenic bacteria.
  • Restriction factor screening identifies RABGAP1L-mediated disruption of endocytosis as a host antiviral defense

    • Sonja Fernbach,
    • Eva E. Spieler,
    • Idoia Busnadiego,
    • Umut Karakus,
    • Anouk Lkharrazi,
    • Silke Stertz,
    • Benjamin G. Hale
    Interferons inhibit viruses through the concerted action of many host restriction factors. Here, Fernbach et al. use siRNA screening to identify interferon-dependent host factors that limit early stages of the influenza A virus replication cycle, leading to the characterization of RABGAP1L-mediated disruption of endocytosis as a broadly acting host antiviral mechanism.
  • Functional interactomes of the Ebola virus polymerase identified by proximity proteomics in the context of viral replication

    • Jingru Fang,
    • Colette Pietzsch,
    • George Tsaprailis,
    • Gogce Crynen,
    • Kelvin Frank Cho,
    • Alice Y. Ting,
    • Alexander Bukreyev,
    • Juan Carlos de la Torre,
    • Erica Ollmann Saphire
    Using proximity proteomics coupled with siRNA screens, Fang et al. reveal functional interactomes of the Ebola virus polymerase, which drives synthesis of viral RNA. These functional hits illuminate a panel of host-dependent regulators of Ebola viral RNA synthesis, which could be potential targets for antiviral drug discovery and development.
  • Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants

    • Yali Zhang,
    • Min Wei,
    • Yangtao Wu,
    • Juan Wang,
    • Yuting Hong,
    • Yang Huang,
    • Lunzhi Yuan,
    • Jian Ma,
    • Kai Wang,
    • Shaojuan Wang,
    • Yang Shi,
    • Zikang Wang,
    • Huilin Guo,
    • Jin Xiao,
    • Chuanlai Yang,
    • Jianghui Ye,
    • Jijing Chen,
    • Yuxi Liu,
    • Baorong Fu,
    • Miaolin Lan,
    • Peixuan Gong,
    • Zehong Huang,
    • Yingying Su,
    • Yixin Chen,
    • Tianying Zhang,
    • Jun Zhang,
    • Huachen Zhu,
    • Hai Yu,
    • Quan Yuan,
    • Tong Cheng,
    • Yi Guan,
    • Ningshao Xia
    Zhang et al. show in vitro cross-species infectivity and neutralization-escape characteristics of 153 SARS-CoV-2 RBD mutants and 11 globally circulating VOCs and VOIs. They reveal an association between enhanced cross-species infection potential and the current cumulative prevalence of mutations, which can inform surveillance and forecasting of SARS-CoV-2 spike mutations.
  • Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting

    • Blake M. Hauser,
    • Maya Sangesland,
    • Kerri J. St. Denis,
    • Evan C. Lam,
    • James Brett Case,
    • Ian W. Windsor,
    • Jared Feldman,
    • Timothy M. Caradonna,
    • Ty Kannegieter,
    • Michael S. Diamond,
    • Alejandro B. Balazs,
    • Daniel Lingwood,
    • Aaron G. Schmidt
    Hauser et al. use structure-guided design to engineer SARS-CoV-2 immunogens that direct immune responses to conserved viral sites in the context of preexisting immunity. In mice, these immunogens elicit antibodies that potently neutralize related coronaviruses, including those of potential pandemic concern. Structural characterization of selected antibodies explains this observation.