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  • DEAH-Box RNA Helicases in Pre-mRNA Splicing
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-11-30
    Francesca De Bortoli; Sara Espinosa; Rui Zhao

    In eukaryotic cells, pre-mRNA splicing is catalyzed by the spliceosome, a highly dynamic molecular machinery that undergoes dramatic conformational and compositional rearrangements throughout the splicing cycle. These crucial rearrangements are largely driven by eight DExD/H-box RNA helicases. Interestingly, the four helicases participating in the late stages of splicing are all DEAH-box helicases

    更新日期:2020-12-01
  • Redox Biochemistry of the Genetic Code
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-11-27
    Bernd Moosmann

    New findings on the chemistry of the amino acids, their role in protein folding, and their sequential primordial introduction have uncovered concealed causalities in genetic code evolution. The genetically encoded amino acids successively provided (i) membrane anchors, (ii) halophilic protein folds, (iii) mesophilic protein folds, (iv) metal ligation, and (v) antioxidation.

    更新日期:2020-11-27
  • Nucleic acid-based technologies targeting coronaviruses
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-11-27
    Thi Khanh Le; Clément Paris; Khadija Shahed Khan; Fran Robson; Wai-Lung Ng; Palma Rocchi

    The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently creating a global health emergency. This crisis is driving a worldwide effort to develop effective vaccines, prophylactics and therapeutics. Nucleic acid (NA)-based treatments hold great potential to combat outbreaks of coronaviruses (CoVs) due to their rapid development

    更新日期:2020-11-27
  • Charting a DNA Repair Roadmap for Immunoglobulin Class Switch Recombination
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-11-26
    Tannishtha Saha; Devakumar Sundaravinayagam; Michela Di Virgilio

    Immunoglobulin (Ig) class switch recombination (CSR) is the process occurring in mature B cells that diversifies the effector component of antibody responses. CSR is initiated by the activity of the B cell-specific enzyme activation-induced cytidine deaminase (AID), which leads to the formation of programmed DNA double-strand breaks (DSBs) at the Ig heavy chain (Igh) locus. Mature B cells use a multilayered

    更新日期:2020-11-27
  • Shedding Light on the Ghost Proteome
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-11-24
    Tristan Cardon; Isabelle Fournier; Michel Salzet

    Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics has led to the identification of proteins translated from alternative open reading frames (AltORFs) in mRNAs. AltORFs are found in addition to predicted reference ORFs and noncoding RNA. Alternative proteins are not represented in the conventional protein

    更新日期:2020-11-25
  • The Trinity of SPRTN Protease Regulation
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-11-09
    Annamaria Ruggiano; Kristijan Ramadan

    The protease SPRTN emerged as the essential enzyme for DNA–protein crosslink proteolysis repair. Biochemical and cell biological work indicated that SPRTN is a nonspecific protease. Recent and independent studies from Lou, Stingele, and Ramadan reveal that SPRTN activity is modulated via three layers of regulation that make it selective for DNA–protein crosslinks.

    更新日期:2020-11-09
  • PAT in the ER for Transmembrane Protein Folding
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-10-17
    Prabuddha S. Pathinayake; Alan C.-Y. Hsu; Peter A.B. Wark

    Integral membrane proteins (IMPs) have crucial roles in many cellular processes. A novel intramembrane chaperone complex, recently elucidated by Chitwood and Hedge, provides mechanistic insight of IMP biogenesis and folding, illustrating how IMPs with multiple transmembrane domains (TMDs) are assembled within the endoplasmic reticulum (ER) membrane.

    更新日期:2020-11-02
  • DNA Processing in the Context of Noncoding Transcription.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-08-27
    Uthra Gowthaman,Desiré García-Pichardo,Yu Jin,Isabel Schwarz,Sebastian Marquardt

    RNA polymerase (RNAP)II frequently transcribes non-protein-coding DNA sequences in eukaryotic genomes into long noncoding RNA (lncRNA). Distinct molecular mechanisms linked to the position of lncRNA relative to the coding gene illustrate how noncoding transcription controls gene expression. Here, we focus on the impact of the act of lncRNA transcription on nearby functional DNA units. We review the

    更新日期:2020-11-02
  • Circular RNAs in Immune Response and Viral Infection.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-06
    Lichong Yan,Y Grace Chen

    Circular RNAs (circRNAs) are a diverse class of RNAs with varying sizes, cellular abundance, and biological functions. Investigations from the past decade have revealed that circRNAs are ubiquitously found in eukaryotes and have defined the different biological roles of circRNAs to illuminate this previously unrecognized class of molecules. In the context of the immune system, immune responses and

    更新日期:2020-11-02
  • Controlling the Controllers: Regulation of Histone Methylation by Phosphosignalling.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-01
    Ryan J Separovich,Chi Nam Ignatius Pang,Marc R Wilkins

    Histone methylation is central to the regulation of eukaryotic transcription. Here, we review how the histone methylation system itself is regulated. There is substantial evidence that mammalian histone methyltransferases and demethylases are phosphorylated and regulated by upstream signalling pathways. Functional studies of specific phosphosites are revealing which kinases and pathways signal to the

    更新日期:2020-11-02
  • Structural and Biophysical Mechanisms of Class C G Protein-Coupled Receptor Function.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-08-26
    Amr Ellaithy,Javier Gonzalez-Maeso,Diomedes A Logothetis,Joshua Levitz

    Groundbreaking structural and spectroscopic studies of class A G protein-coupled receptors (GPCRs), such as rhodopsin and the β2 adrenergic receptor, have provided a picture of how structural rearrangements between transmembrane helices control ligand binding, receptor activation, and effector coupling. However, the activation mechanism of other GPCR classes remains more elusive, in large part due

    更新日期:2020-11-02
  • Nonredundant Roles of GRASP55 and GRASP65 in the Golgi Apparatus and Beyond.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-04
    Xiaoyan Zhang,Yanzhuang Wang

    It has been demonstrated that two Golgi stacking proteins, GRASP55 and GRASP65, self-interact to form trans-oligomers that tether adjacent Golgi membranes into stacks and ribbons in mammalian cells. This ensures proper functioning of the Golgi apparatus in protein trafficking and processing. More recently, GRASP proteins have drawn extensive attention from researchers due to their diverse and essential

    更新日期:2020-11-02
  • The Life Cycle of the Mu-Opioid Receptor
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-10-27
    Javier Cuitavi; Lucía Hipólito; Meritxell Canals

    Opioid receptors (ORs) are undisputed targets for the treatment of pain. Unfortunately, targeting these receptors therapeutically poses significant challenges including addiction, dependence, tolerance, and the appearance of side effects, such as respiratory depression and constipation. Moreover, misuse of prescription and illicit narcotics has resulted in the current opioid crisis. The mu-opioid receptor

    更新日期:2020-10-30
  • Biosynthetic Polymalic Acid as a Delivery Nanoplatform for Translational Cancer Medicine
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-10-22
    Jianguo Zhang; Deyu Chen; Guoxin Liang; Wenrong Xu; Zhimin Tao

    Poly(β-L-malic acid) (PMLA) is a natural polyester produced by numerous microorganisms. Regarding its biosynthetic machinery, a nonribosomal peptide synthetase (NRPS) is proposed to direct polymerization of L-malic acid in vivo. Chemically versatile and biologically compatible, PMLA can be used as an ideal carrier for several molecules, including nucleotides, proteins, chemotherapeutic drugs, and imaging

    更新日期:2020-10-30
  • A Role for N6-Methyladenine in DNA Damage Repair
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-10-16
    Xing Zhang; Robert M. Blumenthal; Xiaodong Cheng

    The leading cause of mutation due to oxidative damage is 8-oxo-2′-deoxyguanosine (8-oxoG) mispairing with adenine (Ade), which can occur in two ways. First, guanine of a G:C DNA base pair can be oxidized. If not repaired in time, DNA polymerases can mispair Ade with 8-oxoG in the template. This 8-oxoG:A can be repaired by enzymes that remove Ade opposite to template 8-oxoG, or 8-oxoG opposite to Cyt

    更新日期:2020-10-17
  • The Integrator Complex in Transcription and Development.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-08-13
    María Saraí Mendoza-Figueroa,Deirdre C Tatomer,Jeremy E Wilusz

    The Integrator complex is conserved across metazoans and controls the fate of many nascent RNAs transcribed by RNA polymerase II (RNAPII). Among the 14 subunits of Integrator is an RNA endonuclease that is crucial for the biogenesis of small nuclear RNAs and enhancer RNAs. Integrator is further employed to trigger premature transcription termination at many protein-coding genes, thereby attenuating

    更新日期:2020-10-16
  • Structures, Mechanisms, and Functions of His-Me Finger Nucleases.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-08-14
    Chyuan-Chuan Wu,Jason L J Lin,Hanna S Yuan

    His-Me finger (also called HNH or ββα-me) nucleases, are a large superfamily of nucleases that share limited sequence homology, but all members carry a highly similar catalytic motif exhibiting a ββα topology. This review represents a structural comparison of His-Me finger nucleases, summarizing their substrate-binding and recognition strategies, mechanisms of enzymatic hydrolysis, cellular functions

    更新日期:2020-10-16
  • Mechanisms of Long Noncoding RNA Nuclear Retention.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-08-13
    Chun-Jie Guo,Guang Xu,Ling-Ling Chen

    Long noncoding RNAs (lncRNAs) are crucial regulators in diverse cellular contexts and biological processes. The subcellular localization of lncRNAs determines their modes of action. Compared to mRNAs, however, many mRNA-like lncRNAs are preferentially localized to the nucleus where they regulate chromatin organization, transcription, and different nuclear condensates. Recent studies have revealed the

    更新日期:2020-10-16
  • Divalent Cations: A Molecular Glue for Protein Materials.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-03
    Hèctor López-Laguna,Julieta Sánchez,Ugutz Unzueta,Ramón Mangues,Esther Vázquez,Antonio Villaverde

    Among inorganic materials, divalent cations modulate thousands of physiological processes that support life. Their roles in protein assembly and aggregation are less known, although they are progressively being brought to light. We review the structural roles of divalent cations here, as well as the novel protein materials that are under development, in which they are used as glue-like agents. More

    更新日期:2020-10-16
  • Balancing the Opposing Principles That Govern Peroxisome Homeostasis
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-10-09
    Shanmuga S. Mahalingam; Nandini Shukla; Jean-Claude Farré; Katarzyna Zientara-Rytter; Suresh Subramani

    Despite major advances in our understanding of players and mechanisms involved in peroxisome biogenesis and peroxisome degradation, very few studies have focused on unraveling the multi-layered connections between, and the coordination of, these two opposing processes that regulate peroxisome homeostasis. The intersection between these processes also provides exciting avenues for future research. This

    更新日期:2020-10-11
  • NCBP3: A Multifaceted Adaptive Regulator of Gene Expression
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-10-05
    Xavier Rambout; Lynne E. Maquat

    Eukaryotic cells have divided the steps of gene expression between their nucleus and cytoplasm. Protein-encoding genes generate mRNAs in the nucleus and mRNAs undergo transport to the cytoplasm for the purpose of producing proteins. Cap-binding protein (CBP)20 and its binding partner CBP80 have been thought to constitute the cap-binding complex (CBC) that is acquired co-transcriptionally by the precursors

    更新日期:2020-10-06
  • Integrins Control Vesicular Trafficking; New Tricks for Old Dogs
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-10-02
    Martijn A. Nolte; Esther N.M. Nolte-'t Hoen; Coert Margadant

    Integrins are transmembrane receptors that transduce biochemical and mechanical signals across the plasma membrane and promote cell adhesion and migration. In addition, integrin adhesion complexes are functionally and structurally linked to components of the intracellular trafficking machinery and accumulating data now reveal that they are key regulators of endocytosis and exocytosis in a variety of

    更新日期:2020-10-02
  • How Lysosomes Sense, Integrate, and Cope with Stress
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-10-01
    Paul Saftig; Rosa Puertollano

    Lysosomes are in the center of the cellular control of catabolic and anabolic processes. These membrane-surrounded acidic organelles contain around 70 hydrolases, 200 membrane proteins, and numerous accessory proteins associated with the cytosolic surface of lysosomes. Accessory and transmembrane proteins assemble in signaling complexes that sense and integrate multiple signals and transmit the information

    更新日期:2020-10-02
  • A Chain of Events: Regulating Target Proteins by SUMO Polymers
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-29
    Nicolette S. Jansen; Alfred C.O. Vertegaal

    Small ubiquitin-like modifiers (SUMOs) regulate virtually all nuclear processes. The fate of the target protein is determined by the architecture of the attached SUMO protein, which can be of polymeric nature. Here, we highlight the multifunctional aspects of dynamic signal transduction by SUMO polymers. The SUMO-targeted ubiquitin ligases (STUbLs) RING-finger protein 4 (RNF4) and RNF111 recognize

    更新日期:2020-09-30
  • YAP and TAZ Are Not Identical Twins.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-24
    Francesca Reggiani,Giulia Gobbi,Alessia Ciarrocchi,Valentina Sancisi

    Yes-associated protein (YAP) and TAZ (WW domain containing transcription regulator 1, or WWTR1) are paralog transcriptional regulators, able to integrate mechanical, metabolic, and signaling inputs to regulate cell growth and differentiation during development and neoplastic progression. YAP and TAZ hold common and distinctive structural features, reflecting only partially overlapping regulatory mechanisms

    更新日期:2020-09-25
  • Galvanization of Protein-Protein Interactions in a Dynamic Zinc Interactome.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-18
    Anna Kocyła,Józef Ba Tran,Artur Krężel

    The presence of Zn2+ at protein–protein interfaces modulates complex function, stability, and introduces structural flexibility/complexity, chemical selectivity, and reversibility driven in a Zn2+-dependent manner. Recent studies have demonstrated that dynamically changing Zn2+ affects numerous cellular processes, including protein–protein communication and protein complex assembly. How Zn2+-involved

    更新日期:2020-09-20
  • Synthesis and Assembly of Virtual Collaborations.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-08-10
    Jacqueline A De Lora,Christina M Termini

    The interplay between academics and society within the environment of the COVID-19 pandemic has impacted on scientists across the world, prompting reevaluation of how virtual toolboxes can be used to support responsible collaborative research practices. We provide awareness of virtual resources and activities that enable scientific discovery using safe and efficient practices.

    更新日期:2020-09-18
  • Alternative Protein Topology-Mediated Evolution of a Catalytic Ribonucleoprotein.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-02
    Lien B Lai,Hong-Duc Phan,Walter J Zahurancik,Venkat Gopalan

    The high-resolution structures of yeast RNase for mitochondrial RNA processing (MRP), a catalytic ribonucleoprotein (RNP), recently reported by Lan et al. and Perederina et al. illustrate how RNA-mediated selection of alternative protein conformations, sampled during stochastic excursions by polymorphic/metamorphic proteins, enabled RNAs and proteins to mutually influence their functional repertoires

    更新日期:2020-09-18
  • The Autophagy-RNA Interplay: Degradation and Beyond.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-08-19
    Marie H Abildgaard,Sólveig H Brynjólfsdóttir,Lisa B Frankel

    Autophagy is a highly conserved degradation pathway that ensures nutrient recycling and removal of unwanted substrates. This process has a fundamental role in stress adaptation and maintenance of cellular homeostasis. Here, we discuss emerging aspects of the autophagy–RNA interplay, including autophagy-mediated degradation of RNA, RNA-binding proteins (RBPs), and ribonucleoprotein (RNP) complexes.

    更新日期:2020-09-18
  • Genetically Encodable Fluorescent and Bioluminescent Biosensors Light Up Signaling Networks.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-07-10
    Xin Zhou,Sohum Mehta,Jin Zhang

    Cell signaling networks are intricately regulated in time and space to determine the responses and fates of cells to different cues. Genetically encodable fluorescent and bioluminescent biosensors enable the direct visualization of these spatiotemporal signaling dynamics within the native biological context, and have therefore become powerful molecular tools whose unique benefits are being used to

    更新日期:2020-09-18
  • Hippo Signaling in Embryogenesis and Development.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-11
    Zhengming Wu,Kun-Liang Guan

    Hippo pathway components are structurally and functionally conserved and are notable for their role in controlling organ size. More diverse functions of the Hippo pathway have been recognized, including development, tissue homeostasis, wound healing and regeneration, immunity, and tumorigenesis. During embryogenesis, different signaling pathways are repeatedly and cooperatively activated, leading to

    更新日期:2020-09-11
  • Inheritance of Histone (H3/H4): A Binary Choice?
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-09
    Nicole J Francis,Djamouna Sihou

    Histones carry information in the form of post-translational modifications (PTMs). For this information to be propagated through cell cycles, parental histones and their PTMs need to be maintained at the same genomic locations. Yet, during DNA replication, every nucleosome in the genome is disrupted to allow passage of the replisome. Recent data have identified histone chaperone activities that are

    更新日期:2020-09-10
  • Protein N-Terminal Acetylation: Structural Basis, Mechanism, Versatility, and Regulation.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-08
    Sunbin Deng,Ronen Marmorstein

    N-terminal acetylation (NTA) is one of the most widespread protein modifications, which occurs on most eukaryotic proteins, but is significantly less common on bacterial and archaea proteins. This modification is carried out by a family of enzymes called N-terminal acetyltransferases (NATs). To date, 12 NATs have been identified, harboring different composition, substrate specificity, and in some cases

    更新日期:2020-09-09
  • Nucleosomes Meet Their Remodeler Match.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-08
    Jonathan Markert,Karolin Luger

    Over 85% of all genomic DNA in eukaryotes is organized in arrays of nucleosomes, the basic organizational principle of chromatin. The tight interaction of DNA with histones represents a significant barrier for all DNA-dependent machineries. This is in part overcome by enzymes, termed ATP-dependent remodelers, that are recruited to nucleosomes at defined locations and modulate their structure. There

    更新日期:2020-09-09
  • Spirits in the Material World: Enhancer RNAs in Transcriptional Regulation.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-09-01
    Tim Y Hou,W Lee Kraus

    Responses to developmental and environmental cues depend on precise spatiotemporal control of gene transcription. Enhancers, which comprise DNA elements bound by regulatory proteins, can activate target genes in response to these external signals. Recent studies have shown that enhancers are transcribed to produce enhancer RNAs (eRNAs). Do eRNAs play a functional role in activating gene expression

    更新日期:2020-09-01
  • Autophagy Assays for Biological Discovery and Therapeutic Development.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-08-21
    Noboru Mizushima,Leon O Murphy

    Autophagy is a lysosome-dependent intracellular degradation system required for various physiological processes and can be dysregulated in human disease. To understand its biological significance and underlying mechanisms, measuring autophagic activity (i.e., autophagic flux) is critical. However, navigating which assays to use, and when, is complicated and at times the results are often interpreted

    更新日期:2020-08-21
  • SLC16 Family: From Atomic Structure to Human Disease.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-08-19
    Patrick D Bosshart,Roch-Philippe Charles,Rachel-Ann A Garibsingh,Avner Schlessinger,Dimitrios Fotiadis

    The solute carrier 16 (SLC16) family represents a diverse group of membrane proteins mediating the transport of monocarboxylates across biological membranes. Family members show a variety of functional roles ranging from nutrient transport and intracellular pH regulation to thyroid hormone homeostasis. Changes in the expression levels and transport function of certain SLC16 transporters are manifested

    更新日期:2020-08-19
  • ER-associated Protein Degradation at Atomic Resolution.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-06-29
    Mohamed A Eldeeb,Richard P Fahlman,Marek Michalak

    The endoplasmic reticulum-associated degradation (ERAD) pathway eliminates misfolded proteins. The Hrd1 complex represents the main gate mediating retrotranslocation of ER luminal misfolded (ERAD-L) substrates to the cytosol. A recent cryo-electron microscopy (cryo-EM) study by Wu et al. unveils the structural features of active Hrd1, providing mechanistic insights into the movement of proteins directed

    更新日期:2020-08-14
  • Phase Separation of RNA Helicase Triggers Stress-Responsive Translational Switch.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-07-01
    Jogender Singh

    A swift response to stress requires global translational suppression, excepting stress proteins. Recently, Iserman et al. uncovered that stress-induced phase separation of the RNA helicase Ded1p results in translational suppression of housekeeping transcripts that contain complex 5′ untranslated regions (UTRs). Stress-response transcripts with simpler 5′ UTRs escape this global translational suppression

    更新日期:2020-08-14
  • Fungal Melanin Rewires Macrophage Metabolism.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-07-01
    Nicolas Papon,Jean-Pierre Gangneux,Yves Delneste

    Aspergillus fumigatus is a deadly fungal pathogen in immunocompromised patients. A report by Gonçalves et al. reveals that melanin, a secondary metabolite present at the surface of infecting fungal spores, induces glycolysis in macrophages to promote inflammatory responses. This opens a window for the development of innovative host-directed antifungal therapies.

    更新日期:2020-08-14
  • Limiting the DNA Double-Strand Break Resectosome for Genome Protection.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-06-06
    Daryl A Ronato,Sofiane Y Mersaoui,Franciele F Busatto,El Bachir Affar,Stéphane Richard,Jean-Yves Masson

    DNA double-strand break (DSB) resection, once thought to be a simple enzymatic process, is emerging as a highly complex series of coordinated activities required to maintain genome integrity. Progress in cell biology, biochemistry, and genetics has deciphered the precise resecting activities, the regulatory components, and their ability to properly channel the resected DNA to the appropriate DNA repair

    更新日期:2020-08-14
  • Current View of Ligand and Lipid Recognition by the Menthol Receptor TRPM8.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-06-09
    Ying Yin,Seok-Yong Lee

    Transient receptor potential (TRP) melastatin member 8 (TRPM8), which is a calcium-permeable ion channel, functions as the primary molecular sensor of cold and menthol in humans. Recent cryoelectron microscopy (cryo-EM) studies of TRPM8 have shown distinct structural features in its architecture and domain assembly compared with the capsaicin receptor TRP vanilloid member 1 (TRPV1). Moreover, ligand-bound

    更新日期:2020-08-14
  • Biomolecular Condensates in the Nucleus.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-07-17
    Benjamin R Sabari,Alessandra Dall'Agnese,Richard A Young

    Nuclear processes such as DNA replication, transcription, and RNA processing each depend on the concerted action of many different protein and RNA molecules. How biomolecules with shared functions find their way to specific locations has been assumed to occur largely by diffusion-mediated collisions. Recent studies have shown that many nuclear processes occur within condensates that compartmentalize

    更新日期:2020-07-17
  • Re-Evaluating the Conventional Wisdom about Binding Assays.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-05-10
    Brandon D Wilson,H Tom Soh

    Analytical technologies based on binding assays have evolved substantially since their inception nearly 60 years ago, but our conceptual understanding of molecular recognition has not kept pace. Contemporary technologies, such as single-molecule and digital measurements, have challenged, or even rendered obsolete, core concepts behind conventional binding assay design. Here, we explore the fundamental

    更新日期:2020-07-16
  • Cytosolic Events in the Biogenesis of Mitochondrial Proteins.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-05-11
    Yury S Bykov,Doron Rapaport,Johannes M Herrmann,Maya Schuldiner

    While targeting of proteins synthesized in the cytosol to any organelle is complex, mitochondria present the most challenging of destinations. First, import of nuclear-encoded proteins needs to be balanced with production of mitochondrial-encoded ones. Moreover, as mitochondria are divided into distinct subdomains, their proteins harbor a number of different targeting signals and biophysical properties

    更新日期:2020-07-16
  • Making the Case for Disordered Proteins and Biomolecular Condensates in Bacteria.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-05-23
    Megan C Cohan,Rohit V Pappu

    Intrinsically disordered proteins/regions (IDPs/IDRs) contribute to a diverse array of molecular functions in eukaryotic systems. There is also growing recognition that membraneless biomolecular condensates, many of which are organized or regulated by IDPs/IDRs, can enable spatial and temporal regulation of complex biochemical reactions in eukaryotes. Motivated by these findings, we assess if (and

    更新日期:2020-07-16
  • Coupling of Ribosome Synthesis and Translational Capacity with Cell Growth.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-05-21
    Xiongfeng Dai,Manlu Zhu

    Ribosome and protein synthesis lie at the core of cell growth and are major consumers of the cellular budget. Here we review recent progress in the coupling of ribosome synthesis and translational capacity with cell growth in bacteria. We elaborate on the different strategies of bacteria to modulate the protein synthesis rate at fast and slow growth rates. In particular, bacterial cells maintain translational

    更新日期:2020-07-16
  • Emerging Insights into the Structure and Function of Complement C5a Receptors.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-05-10
    Shubhi Pandey,Jagannath Maharana,Xaria X Li,Trent M Woodruff,Arun K Shukla

    Complement factor C5a is an integral constituent of the complement cascade critically involved in the innate immune response, and it exerts its functions via two distinct receptors, C5aR1 and C5aR2. While C5aR1 is a prototypical G-protein-coupled receptor (GPCR), C5aR2 lacks functional coupling to heterotrimeric G proteins, although both receptors efficiently recruit β arrestins (βarrs). Here, we discuss

    更新日期:2020-07-16
  • The Wide World of Coacervates: From the Sea to Neurodegeneration.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-05-13
    Emanuele Astoricchio,Caterina Alfano,Lawrence Rajendran,Piero Andrea Temussi,Annalisa Pastore

    The formation of immiscible liquid phases or coacervates is a phenomenon widely observed in biology. Marine organisms, for instance, use liquid–liquid phase separation (LLPS) as the precursor phase to form various fibrillar or crustaceous materials that are essential for surface adhesion. More recently, the importance of LLPS has been realized in the compartmentalization of living cells and in obtaining

    更新日期:2020-07-16
  • Molecular Mechanisms of Lysosome and Nucleus Communication.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-07-02
    Qian Zhao,Shihong Max Gao,Meng C Wang

    Lysosomes transcend the role of degradation stations, acting as key nodes for interorganelle crosstalk and signal transduction. Lysosomes communicate with the nucleus through physical proximity and functional interaction. In response to external and internal stimuli, lysosomes actively adjust their distribution between peripheral and perinuclear regions and modulate lysosome–nucleus signaling pathways;

    更新日期:2020-07-02
  • A Tale of Two Moieties: Rapidly Evolving CRISPR/Cas-Based Genome Editing.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-06-30
    Li Yang,Jia Chen

    Two major moieties in genome editing are required for precise genetic changes: the locator moiety for target binding and the effector moiety for genetic engineering. By taking advantage of CRISPR/Cas, which consists of different modules for independent target binding and cleavage, a spectrum of precise and versatile genome editing technologies have been developed for broad applications in biomedical

    更新日期:2020-06-30
  • 更新日期:2020-06-26
  • Location, Location, Location: Compartmentalization of NAD+ Synthesis and Functions in Mammalian Cells.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-06-25
    Xiaolu A Cambronne,W Lee Kraus

    The numerous biological roles of NAD+ are organized and coordinated via its compartmentalization within cells. The spatial and temporal partitioning of this intermediary metabolite is intrinsic to understanding the impact of NAD+ on cellular signaling and metabolism. We review evidence supporting the compartmentalization of steady-state NAD+ levels in cells, as well as how the modulation of NAD+ synthesis

    更新日期:2020-06-25
  • 更新日期:2020-06-16
  • Emerging Roles of tRNAs in RNA Virus Infections.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-06-03
    Alexandre Nunes,Diana Roberta Ribeiro,Mariana Marques,Manuel A S Santos,Daniela Ribeiro,Ana Raquel Soares

    Viruses rely on the host cell translation machinery for efficient synthesis of their own proteins. Emerging evidence highlights different roles for host transfer RNAs (tRNAs) in the process of virus replication. For instance, different RNA viruses manipulate host tRNA pools to favor viral protein translation. Interestingly, specific host tRNAs are used as reverse transcription primers and are packaged

    更新日期:2020-06-03
  • Nothing Is Yet Set in (Hi)stone: Novel Post-Translational Modifications Regulating Chromatin Function.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-06-01
    Jennifer C Chan,Ian Maze

    Histone post-translational modifications (PTMs) have emerged as exciting mechanisms of biological regulation, impacting pathways related to cancer, immunity, brain function, and more. Over the past decade alone, several histone PTMs have been discovered, including acylation, lipidation, monoaminylation, and glycation, many of which appear to have crucial roles in nucleosome stability and transcriptional

    更新日期:2020-06-01
  • Complementarity of Hydrogen/Deuterium Exchange Mass Spectrometry and Cryo-Electron Microscopy.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-05-30
    John R Engen,Elizabeth A Komives

    Methodological improvements in both single particle cryo-electron microscopy (cryo-EM) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) mean that the two methods are being more frequently used together to tackle complex problems in structural biology. There are many benefits to this combination, including for the analysis of low-resolution density, for structural validation, in the analysis

    更新日期:2020-05-30
  • Detecting Protein-Small Molecule Interactions Using Limited Proteolysis-Mass Spectrometry (LiP-MS).
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-05-29
    Monika Pepelnjak,Natalie de Souza,Paola Picotti

    更新日期:2020-05-29
  • Chaperone Machineries of Rubisco - The Most Abundant Enzyme.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-05-26
    Manajit Hayer-Hartl,F Ulrich Hartl

    A major challenge faced by human civilization is to ensure that agricultural productivity keeps pace with population growth and a changing climate. All food supply is generated, directly or indirectly, through the process of photosynthesis, with the enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzing the assimilation of atmospheric CO2. Despite its pivotal role, Rubisco is a

    更新日期:2020-05-26
  • Managing Hyperosmotic Stress through Phase Separation.
    Trends Biochem. Sci. (IF 14.732) Pub Date : 2020-05-21
    Ivan Peran,Nafiseh Sabri,Tanja Mittag

    In a recent study, Yasuda et al. show how liquid–liquid phase separation (LLPS) under hyperosmotic stress conditions allows cells to react to ubiquitinated proteins and to assemble nuclear, liquid compartments that recruit proteasomes and result in aggregate clearance.

    更新日期:2020-05-21
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