Abstract：
:Proper gene expression is essential for the survival of every cell. Once thought to be a passive transporter of genetic information, RNA has recently emerged as a key player in nearly every pathway in the cell. A full description of its structure is critical to understanding RNA function. Decades of research have focused on utilizing chemical tools to interrogate the structures of RNAs, with recent focus shifting to performing experiments inside living cells. This Review will detail the design and utility of chemical reagents used in RNA structure probing. We also outline how these reagents have been used to gain a deeper understanding of RNA structure in vivo. We review the recent merger of chemical probing with deep sequencing. Finally, we outline some of the hurdles that remain in fully characterizing the structure of RNA inside living cells, and how chemical biology can uniquely tackle such challenges.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Kubota M,Tran C,Spitale RCdoi
10.1038/nchembio.1958subject
Has Abstractpub_date
2015-12-01 00:00:00pages
933-41issue
12eissn
1552-4450issn
1552-4469pii
nchembio.1958journal_volume
11pub_type
杂志文章,评审abstract：:Biodiversity, or the relative abundance of species, measures the persistence of an ecosystem. To better understand its modulation, we analyzed the spatial and temporal dynamics of a synthetic, chemical-mediated ecosystem that consisted of two engineered Escherichia coli populations. Depending on the specific experimen...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.244
更新日期：2009-12-01 00:00:00
abstract：:Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2538
更新日期：2018-02-01 00:00:00
abstract：:The simultaneous observation of interdependent reactions within different phases as catalyzed by membrane-bound enzymes is still a challenging task. One such enzyme, the Escherichia coli integral membrane protein diacylglycerol kinase (DGK), is a key player in lipid regulation. It catalyzes the generation of phosphati...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.543
更新日期：2011-05-01 00:00:00
abstract：:The streptothricin (ST) antibiotics, produced by Streptomyces bacteria, contain L-β-lysine ((3S)-3,6-diaminohexanoic acid) oligopeptides as pendant chains. Here we describe three unusual nonribosomal peptide synthetases (NRPSs) involved in ST biosynthesis: ORF 5 (a stand-alone adenylation (A) domain), ORF 18 (containi...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1040
更新日期：2012-09-01 00:00:00
abstract：:DNA polymerases catalyze efficient and high-fidelity DNA synthesis. While this reaction favors nucleotide incorporation, polymerases also catalyze a reverse reaction, pyrophosphorolysis, that removes the DNA primer terminus and generates deoxynucleoside triphosphates. Because pyrophosphorolysis can influence polymeras...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2450
更新日期：2017-10-01 00:00:00
abstract：:Synthetic mRNA is an attractive vehicle for gene therapies because of its transient nature and improved safety profile over DNA. However, unlike DNA, broadly applicable methods to control expression from mRNA are lacking. Here we describe a platform for small-molecule-based regulation of expression from modified RNA (...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-018-0146-9
更新日期：2018-11-01 00:00:00
abstract：:Small-molecule inhibitors of kinesin-5 (refs. 1-3), a protein essential for eukaryotic cell division, represent alternatives to antimitotic agents that target tubulin. While tubulin is needed for multiple intracellular processes, the known functions of kinesin-5 are limited to dividing cells, making it likely that kin...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio812
更新日期：2006-09-01 00:00:00
abstract：:Ferroptosis is a form of regulated necrotic cell death controlled by glutathione peroxidase 4 (GPX4). At present, mechanisms that could predict sensitivity and/or resistance and that may be exploited to modulate ferroptosis are needed. We applied two independent approaches-a genome-wide CRISPR-based genetic screen and...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2239
更新日期：2017-01-01 00:00:00
abstract：:CRISPR-Cas9 has emerged as a powerful technology that enables ready modification of the mammalian genome. The ability to modulate Cas9 activity can reduce off-target cleavage and facilitate precise genome engineering. Here we report the development of a Cas9 variant whose activity can be switched on and off in human c...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2179
更新日期：2016-11-01 00:00:00
abstract：:Intrinsically disordered regions (IDRs) of proteins often regulate function upon post-translational modification (PTM) through interactions with folded domains. An IDR linking two α-helices (α1-α2) of the antiapoptotic protein Bcl-xL experiences several PTMs that reduce antiapoptotic activity. Here, we report that PTM...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-018-0011-x
更新日期：2018-05-01 00:00:00
abstract：:Controlled distribution of lipids across various cell membranes is crucial for cell homeostasis and regulation. We developed an imaging method that allows simultaneous in situ quantification of cholesterol in two leaflets of the plasma membrane (PM) using tunable orthogonal cholesterol sensors. Our imaging revealed ma...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2268
更新日期：2017-03-01 00:00:00
abstract：:Learning regulatory networks from genomics data is an important problem with applications spanning all of biology and biomedicine. Functional genomics projects offer a cost-effective means of greatly expanding the completeness of our regulatory models, and for some prokaryotic organisms they offer a means of learning ...
journal_title：Nature chemical biology
pub_type： 杂志文章,评审
doi：10.1038/nchembio.122
更新日期：2008-11-01 00:00:00
abstract：:Drug discovery resources in academia and industry are not used efficiently, to the detriment of industry and society. Duplication could be reduced, and productivity could be increased, by performing basic biology and clinical proofs of concept within open access industry-academia partnerships. Chemical biologists coul...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio0709-436
更新日期：2009-07-01 00:00:00
abstract：:The function of many biologically active molecules requires the presence of carbon-nitrogen bonds in strategic positions. The biosynthetic pathways leading to such bonds can be bypassed through chemical synthesis to synthesize natural products more efficiently and also to generate the molecular diversity unavailable i...
journal_title：Nature chemical biology
pub_type： 杂志文章,评审
doi：10.1038/nchembio0606-284
更新日期：2006-06-01 00:00:00
abstract：:Methods to evolve synthetic, rather than biological, polymers could significantly expand the functional potential of polymers that emerge from in vitro evolution. Requirements for synthetic polymer evolution include (i) sequence-specific polymerization of synthetic building blocks on an amplifiable template, (ii) disp...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.280
更新日期：2010-02-01 00:00:00
abstract：:Long noncoding RNAs (lncRNAs) are important for gene expression, but little is known about their structures. RepA is a 1.6-kb mouse lncRNA comprising the same sequence as the 5' region of Xist, including A and F repeats. It has been proposed to facilitate the initiation and spread of X-chromosome inactivation, althoug...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2272
更新日期：2017-03-01 00:00:00
abstract：:Sulfoquinovose is produced by photosynthetic organisms at a rate of 10(10) tons per annum and is degraded by bacteria as a source of carbon and sulfur. We have identified Escherichia coli YihQ as the first dedicated sulfoquinovosidase and the gateway enzyme to sulfoglycolytic pathways. Structural and mutagenesis studi...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2023
更新日期：2016-04-01 00:00:00
abstract：:Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug pyridostatin promotes growth arr...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.780
更新日期：2012-02-05 00:00:00
abstract：:Targeted drugs are effective when they directly inhibit strong disease drivers, but only a small fraction of diseases feature defined actionable drivers. Alternatively, network-based approaches can uncover new therapeutic opportunities. Applying an integrated phenotypic screening, chemical and phosphoproteomics strate...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2489
更新日期：2017-12-01 00:00:00
abstract：:We document a new dimension of surface recognition in which communication is controlled through the collective behavior of lipids. Membrane cholesterol induces a tilt in glycolipid receptor headgroup, resulting in loss of access for ligand binding. This property appears to organize erythrocyte blood group presentation...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.551
更新日期：2011-05-01 00:00:00
abstract：:Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV c...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2537
更新日期：2018-02-01 00:00:00
abstract：:We identify an Arabidopsis pyridoxal-phosphate-dependent aminotransferase, VAS1, whose loss-of-function simultaneously increases amounts of the phytohormone auxin and the ethylene precursor 1-aminocyclopropane-1-carboxylate. VAS1 uses the ethylene biosynthetic intermediate methionine as an amino donor and the auxin bi...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1178
更新日期：2013-04-01 00:00:00
abstract：:Nitric oxide (NO) signaling through the formation of cGMP is well established; however, there seems to be an increasing role for cGMP-independent NO signaling. Although key molecular details remain unanswered, S-nitrosation represents an example of cGMP-independent NO signaling. This modification has garnered recent a...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio720
更新日期：2005-08-01 00:00:00
abstract：:Designing selective inhibitors of proteases has proven problematic, in part because pharmacophores that confer potency exploit the conserved catalytic apparatus. We developed a fundamentally different approach by designing irreversible inhibitors that target noncatalytic cysteines that are structurally unique to a tar...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.492
更新日期：2011-01-01 00:00:00
abstract：:Nonribosomal peptide antibiotics, including polymyxin, vancomycin, and teixobactin, most of which contain D-amino acids, are highly effective against multidrug-resistant bacteria. However, overusing antibiotics while ignoring the risk of resistance arising has inexorably led to widespread emergence of resistant bacter...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-018-0009-4
更新日期：2018-04-01 00:00:00
abstract：:Changes in the cellular environment modulate protein energy landscapes to drive important biology, with consequences for signaling, allostery and other vital processes. The effects of ubiquitination are particularly important because of their potential influence on degradation by the 26S proteasome. Moreover, proteaso...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-020-0556-3
更新日期：2020-08-01 00:00:00
abstract：: ...
journal_title：Nature chemical biology
pub_type： 评论,杂志文章
doi：10.1038/s41589-018-0073-9
更新日期：2018-06-01 00:00:00
abstract：:RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-su...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2228
更新日期：2017-01-01 00:00:00
abstract：:Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome....
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2370
更新日期：2017-07-01 00:00:00
abstract：:Bioinorganic chemistry remains a vibrant discipline at the interface of chemistry and the biological sciences. Metal ions function in numerous metalloenzymes, are incorporated into pharmaceuticals and imaging agents, and inspire the synthesis of catalysts used to achieve many chemical transformations. ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio1006-504
更新日期：2006-10-01 00:00:00
