Abstract:
:Genetically encoded biosensors are useful tools for detecting the presence and levels of diverse biomolecules in living cells. However, low-abundance targets are difficult to detect because they are often unable to bind and activate enough biosensors to detect using standard microscopic imaging approaches. Here we describe a type of RNA-based biosensor, an RNA integrator, which enables detection of low-abundance targets in vitro and in living cells. The RNA integrator is an RNA sequence comprising a ribozyme and an unfolded form of the fluorogenic aptamer Broccoli. Upon binding its target, the ribozyme undergoes cleavage and releases Broccoli, which subsequently folds and becomes fluorescent. Importantly, each target molecule can bind and induce cleavage of multiple copies of the integrator sensor, resulting in an amplified signal. We show that this approach can be generalized to numerous different ribozyme types for the detection of various small molecules.
journal_name
Cell Chem Bioljournal_title
Cell chemical biologyauthors
You M,Litke JL,Wu R,Jaffrey SRdoi
10.1016/j.chembiol.2019.01.005subject
Has Abstractpub_date
2019-04-18 00:00:00pages
471-481.e3issue
4eissn
2451-9456issn
2451-9448pii
S2451-9456(19)30027-3journal_volume
26pub_type
杂志文章abstract::Alternative polyadenylation (APA) plays a critical role in regulating gene expression. However, the balance between genome-encoded APA processing and autoregulation by APA modulating RNA binding protein (RBP) factors is not well understood. We discovered two potent small-molecule modulators of APA (T4 and T5) that pro...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2018.09.006
更新日期:2018-12-20 00:00:00
abstract::H2S-producing enzymes in bacteria have been shown to be closely engaged in the process of microbial survival and antibiotic resistance. However, no inhibitors have been discovered for these enzymes, e.g., 3-mercaptopyruvate sulfurtransferase (MST). In the present study, we identified several classes of inhibitors for ...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2020.10.012
更新日期:2020-12-17 00:00:00
abstract::In this issue of Cell Chemical Biology, Diaz et al. (2017) report a strategy to achieve temporal, spatial, and stoichiometric control over the protein kinase cAbl in living cells. They achieve this by splitting cAbl into two inactive fragments that form an active kinase upon small molecule addition, potentially provid...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2017.10.004
更新日期:2017-10-19 00:00:00
abstract::ATP is an important energy metabolite and allosteric signal in health and disease. ATP-interacting proteins, such as P2 receptors, control inflammation, cell death, migration, and wound healing. However, identification of allosteric ATP sites remains challenging, and our current inventory of ATP-controlled pathways is...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2020.05.010
更新日期:2020-08-20 00:00:00
abstract::Antibiotic resistance is a rapidly evolving health concern that requires a sustained effort to understand mechanisms of resistance and to develop new agents that overcome those mechanisms. The dihydrofolate reductase (DHFR) inhibitor, trimethoprim (TMP), remains one of the most important orally administered antibiotic...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.11.007
更新日期:2016-12-22 00:00:00
abstract::The natural product cepafungin I was recently reported to be one of the most potent covalent inhibitors of the 20S proteasome core particle through a series of in vitro activity assays. Here, we report a short chemoenzymatic total synthesis of cepafungin I featuring the use of a regioselective enzymatic oxidation to p...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2020.07.012
更新日期:2020-10-15 00:00:00
abstract::Eicosanoids and related oxylipins are critical, small bioactive mediators of human physiology and inflammation. While ∼1,100 distinct species have been predicted to exist, to date, less than 150 of these molecules have been measured in humans, limiting our understanding of their role in human biology. Using a directed...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2018.11.015
更新日期:2019-03-21 00:00:00
abstract::Kinase inhibitors are effective cancer therapies. Unfortunately, drug resistance emerges in response to kinase inhibition leading to loss of drug efficacy. In this issue of Cell Chemical Biology, Peh et al. (2018) demonstrate that caspase activators effectively delay onset of resistance to kinase inhibitors and are ex...
journal_title:Cell chemical biology
pub_type: 评论,杂志文章
doi:10.1016/j.chembiol.2018.08.001
更新日期:2018-08-16 00:00:00
abstract::The rise of antibiotic resistance threatens modern medicine; to combat it new diagnostic methods are required. Sequencing the whole genome of a pathogen offers the potential to accurately determine which antibiotics will be effective to treat a patient. A key limitation of this approach is that it cannot classify rare...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2017.12.009
更新日期:2018-03-15 00:00:00
abstract::Small-molecule targeted recruitment of nucleases to RNA is a powerful method to affect RNA biology. Inforna, a sequence-based design approach to target RNA, enables the design of small molecules that bind to and cleave RNA in a selective and substoichiometric manner. Here, we investigate the ability of RNA-targeted de...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2019.04.008
更新日期:2019-08-15 00:00:00
abstract::Acyl-coenzyme A (CoA)/protein interactions are essential for life. Despite this importance, their global scope and selectivity remains undefined. Here, we describe CATNIP (CoA/AcetylTraNsferase Interaction Profiling), a chemoproteomic platform for the high-throughput analysis of acyl-CoA/protein interactions in endoge...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2019.11.011
更新日期:2020-03-19 00:00:00
abstract::Activation of innate immune signaling in the tumor microenvironment is central to a successful anti-tumor immune response, and it is in large part mediated by cytosolic double-stranded DNA sensing. Here, Carozza et al. (2020b) report potent and selective inhibitors of ENPP1, a negative regulator of innate immune signa...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2020.11.001
更新日期:2020-11-19 00:00:00
abstract::The accumulation of α-synuclein amyloid fibrils in the brain is linked to Parkinson's disease and other synucleinopathies. The intermediate species in the early aggregation phase of α-synuclein are involved in the emergence of amyloid toxicity and considered to be the most neurotoxic. The N-terminal region flanking th...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2020.12.010
更新日期:2021-01-06 00:00:00
abstract::The unique photophysical properties of lanthanides, such as europium, terbium, and ytterbium, make them versatile molecular probes of biological systems. In particular, their long-lived photoluminescence, narrow bandwidth emissions, and large Stokes shifts enable experiments that are infeasible with organic fluorophor...
journal_title:Cell chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.chembiol.2020.07.009
更新日期:2020-08-20 00:00:00
abstract::Disorders of bone healing and remodeling are indications with an unmet need for effective pharmacological modulators. We used a high-throughput screen to identify activators of the bone marker alkaline phosphatase (ALP), and discovered 6,8-dimethyl-3-(4-phenyl-1H-imidazol-5-yl)quinolin-2(1H)-one (DIPQUO). DIPQUO marke...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2019.03.009
更新日期:2019-07-18 00:00:00
abstract::Janus kinases (JAKs) are a family of cytoplasmatic tyrosine kinases that are attractive targets for the development of anti-inflammatory drugs given their roles in cytokine signaling. One question regarding JAKs and their inhibitors that remains under intensive debate is whether JAK inhibitors should be isoform select...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.10.008
更新日期:2016-11-17 00:00:00
abstract::There is a scarcity of pharmacological tools to interrogate protein kinase function in Plasmodium parasites, the causative agent of malaria. Among Plasmodium's protein kinases, those characterized as atypical represent attractive drug targets as they lack sequence similarity to human proteins. Here, we describe takini...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2018.11.003
更新日期:2019-03-21 00:00:00
abstract::Non-ribosomal peptides (NRPs) are biosynthesized on non-ribosomal peptides synthetase (NRPS) complexes, of which a C-terminal releasing domain commonly offloads the products. Interestingly, a dedicated releasing domain is absent in surugamides (SGM) NRPS, which directs the biosynthesis of cyclic octapeptides, SGM-A to...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2019.02.010
更新日期:2019-05-16 00:00:00
abstract::Dengue virus infects more than 300 million people annually, yet there is no widely protective vaccine or drugs against the virus. Efforts to develop antivirals against classical targets such as the viral protease and polymerase have not yielded drugs that have advanced to the clinic. Here, we show that the allosteric ...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.03.010
更新日期:2016-04-21 00:00:00
abstract::A picture may speak a thousand words, but if those words fail to form a coherent sentence there is little to be learned. As cutting-edge imaging technology now provides us the tools to decipher the multitude of roles played by metals and metalloids in molecular, cellular, and developmental biology, as well as health a...
journal_title:Cell chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.chembiol.2017.10.006
更新日期:2018-01-18 00:00:00
abstract::Using light to control cellular processes is one of the attractive areas of research. Here, availability of different, light-responsive caged compounds has played a critical role. In this issue of Cell Chemical Biology, Hövelmann et al. (2016) give us an example of how to design and use caged lipids to guide chemotaxi...
journal_title:Cell chemical biology
pub_type: 评论,杂志文章
doi:10.1016/j.chembiol.2016.05.003
更新日期:2016-05-19 00:00:00
abstract::Interferon-induced transmembrane protein 3 (IFITM3) is a key interferon effector that broadly prevents infection by diverse viruses. However, the cellular factors that control IFITM3 homeostasis and antiviral activity have not been fully elucidated. Using site-specific photo-crosslinking and quantitative proteomic ana...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2020.03.004
更新日期:2020-05-21 00:00:00
abstract::KRAS is frequently mutated in several of the most lethal types of cancer; however, the KRAS protein has proven a challenging drug target. K-RAS4B must be localized to the plasma membrane by prenylation to activate oncogenic signaling, thus we endeavored to target the protein-membrane interface with small-molecule comp...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2018.07.009
更新日期:2018-11-15 00:00:00
abstract::Rhomboid-family intramembrane proteases regulate important biological processes and have been associated with malaria, cancer, and Parkinson's disease. However, due to the lack of potent, selective, and pharmacologically compliant inhibitors, the wide therapeutic potential of rhomboids is currently untapped. Here, we ...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2017.09.007
更新日期:2017-12-21 00:00:00
abstract::Disease sites in atherosclerosis and cancer feature cell masses (e.g., plaques/tumors), a low pH extracellular microenvironment, and various pro-inflammatory cytokines such as tumor necrosis factor α (TNFα). The ability to engineer a cell to seek TNFα sources allows for targeted therapeutic delivery. To accomplish thi...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2017.05.008
更新日期:2017-06-22 00:00:00
abstract::G-quadruplexes are specialized secondary structures in nucleic acids that possess significant conformational polymorphisms. The precise G-quadruplex conformations in vivo and their relevance to biological functions remain controversial and unclear, especially for telomeric G-quadruplexes. Here, we report a novel singl...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.08.013
更新日期:2016-10-20 00:00:00
abstract::Increased telomerase activity is associated with malignancy and poor prognosis in human cancer, but the development of targeted agents has not yet provided clinical benefit. Here we report that, instead of targeting the telomerase enzyme directly, small molecules that bind to the G-hairpin of the hTERT G-quadruplex-fo...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2019.04.009
更新日期:2019-08-15 00:00:00
abstract::Clostridium difficile causes increasing numbers of life-threatening intestinal infections. Symptoms associated with C. difficile infection (CDI) are mediated by secreted protein toxins, whose virulence is modulated by intracellular auto-proteolysis following allosteric activation of their protease domains by inositol ...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2018.10.002
更新日期:2019-01-17 00:00:00
abstract::Energy coupling factor (ECF) transporters are responsible for the uptake of essential scarce nutrients in prokaryotes. This ATP-binding cassette transporter family comprises two subgroups that share a common architecture forming a tripartite membrane protein complex consisting of a translocation component and ATP hydr...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.06.008
更新日期:2016-07-21 00:00:00
abstract::Epidermal growth factor receptor (EGFR) is a target of signal-derived H2O2, and oxidation of active-site cysteine 797 to sulfenic acid enhances kinase activity. Although a major class of covalent drugs targets C797, nothing is known about its catalytic importance or how S-sulfenylation leads to activation. Here, we re...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.05.017
更新日期:2016-07-21 00:00:00