Abstract：
:MicroRNAs are evolutionarily conserved small, noncoding RNAs that regulate diverse biological processes. Due to their essential regulatory roles, microRNA biogenesis is tightly regulated, where protein factors are often found to interact with specific primary and precursor microRNAs for regulation. Here, using NMR relaxation dispersion spectroscopy and mutagenesis, we reveal that the precursor of oncogenic microRNA-21 exists as a pH-dependent ensemble that spontaneously reshuffles the secondary structure of the entire apical stem-loop region, including the Dicer cleavage site. We show that the alternative excited conformation transiently sequesters the bulged adenine into a noncanonical protonated A+-G mismatch, conferring a substantial enhancement in Dicer processing over its ground conformational state. These results indicate that microRNA maturation efficiency may be encoded in the intrinsic dynamic ensemble of primary and precursor microRNAs, providing a potential means of regulating microRNA biogenesis in response to environmental and cellular stimuli.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Baisden JT,Boyer JA,Zhao B,Hammond SM,Zhang Qdoi
10.1038/s41589-020-00667-5subject
Has Abstractpub_date
2021-01-01 00:00:00pages
80-88issue
1eissn
1552-4450issn
1552-4469pii
10.1038/s41589-020-00667-5journal_volume
17pub_type
杂志文章abstract：:5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1848
更新日期：2015-08-01 00:00:00
abstract：:Identifying targets of antibacterial compounds remains a challenging step in the development of antibiotics. We have developed a two-pronged functional genomics approach to predict mechanism of action that uses mutant fitness data from antibiotic-treated transposon libraries containing both upregulation and inactivati...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-018-0041-4
更新日期：2018-06-01 00:00:00
abstract：:Excessive aggregation of proteins has a major impact on cell fate and is a hallmark of amyloid diseases in humans. To resolve insoluble deposits and to maintain protein homeostasis, all cells use dedicated protein disaggregation, protein folding and protein degradation factors. Despite intense recent research, the und...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1931
更新日期：2015-11-01 00:00:00
abstract：:Enzyme-catalyzed peptide ligation is a powerful tool for site-specific protein bioconjugation, but stringent enzyme-substrate specificity limits its utility. We developed an approach for comprehensively characterizing peptide ligase specificity for N termini using proteome-derived peptide libraries. We used this strat...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2521
更新日期：2018-01-01 00:00:00
abstract：:Signal transduction, regulatory processes and pharmaceutical responses are highly dependent upon ligand residence times. Gaining insight into how physical factors influence residence times (1/k(off)) should enhance our ability to manipulate biological interactions. We report experiments that yield structural insight i...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.769
更新日期：2012-01-15 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：:Oxidase and oxygenase enzymes allow the use of relatively unreactive O2 in biochemical reactions. Many of the mechanistic strategies used in nature for this key reaction are represented within the 2-histidine-1-carboxylate facial triad family of non-heme Fe(II)-containing enzymes. The open face of the metal coordinati...
journal_title：Nature chemical biology
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更新日期：2008-03-01 00:00:00
abstract：:Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoy...
journal_title：Nature chemical biology
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journal_title：Nature chemical biology
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更新日期：2006-09-01 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
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更新日期：2012-02-05 00:00:00
abstract：:Only 25% of bacterial membrane transporters have functional annotation owing to the difficulty of experimental study and of accurate prediction of their function. Here we report a sequence-independent method for high-throughput mining of novel transporters. The method is based on ligand-responsive biosensor systems th...
journal_title：Nature chemical biology
pub_type： 杂志文章
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更新日期：2016-12-01 00:00:00
abstract：:The serotonin6 receptor (5-HT6R) is a promising target for treating cognitive deficits of schizophrenia often linked to alterations of neuronal development. This receptor controls neurodevelopmental processes, but the signaling mechanisms involved remain poorly understood. Using a proteomic strategy, we show that 5-HT...
journal_title：Nature chemical biology
pub_type： 杂志文章
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更新日期：2014-07-01 00:00:00
abstract：:Binding to the primary receptor, CD4, triggers conformational changes in the metastable HIV-1 envelope glycoprotein (Env) trimer ((gp120-gp41)3) that are important for virus entry into host cells. These changes include an 'opening' of the trimer, creation of a binding site for the CCR5 co-receptor and formation and/or...
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pub_type： 杂志文章
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更新日期：2014-10-01 00:00:00
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journal_title：Nature chemical biology
pub_type： 杂志文章,评审
doi：10.1038/nchembio.1558
更新日期：2014-07-01 00:00:00
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journal_title：Nature chemical biology
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更新日期：2007-02-01 00:00:00
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journal_title：Nature chemical biology
pub_type： 杂志文章
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更新日期：2012-07-01 00:00:00
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journal_title：Nature chemical biology
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更新日期：2011-10-16 00:00:00
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journal_title：Nature chemical biology
pub_type： 杂志文章,评审
doi：10.1038/nchembio.1158
更新日期：2013-03-01 00:00:00
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journal_title：Nature chemical biology
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更新日期：2012-04-01 00:00:00
abstract：:Combination antiretroviral therapy has transformed HIV-1 infection, once a fatal illness, into a manageable chronic condition. Drug resistance, severe side effects and treatment noncompliance bring challenges to combination antiretroviral therapy implementation in clinical settings and indicate the need for additional...
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更新日期：2016-10-01 00:00:00
abstract：:Genetic screens in cultured human cells represent a powerful unbiased strategy to identify cellular pathways that determine drug efficacy, providing critical information for clinical development. We used insertional mutagenesis-based screens in haploid cells to identify genes required for the sensitivity to lasonolide...
journal_title：Nature chemical biology
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更新日期：2020-02-01 00:00:00
abstract：:Mycobacterium tuberculosis and Yersinia pestis, the causative agents of tuberculosis and plague, respectively, are pathogens with serious ongoing impact on global public health and potential use as agents of bioterrorism. Both pathogens have iron acquisition systems based on siderophores, secreted iron-chelating compo...
journal_title：Nature chemical biology
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更新日期：2005-06-01 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
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更新日期：2006-10-01 00:00:00
abstract：:SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor (D2R), but it contains structural features associated with orthosteric D2R antagonists. Using a functional complementation system to control the identity of individual protomers within a dimeric D2R complex, we converted ...
journal_title：Nature chemical biology
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更新日期：2014-09-01 00:00:00
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journal_title：Nature chemical biology
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journal_title：Nature chemical biology
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abstract：:Tyrian purple, mainly composed of 6,6'-dibromoindigo (6BrIG), is an ancient dye extracted from sea snails and was recently demonstrated as a biocompatible semiconductor material. However, its synthesis remains limited due to uncharacterized biosynthetic pathways and the difficulty of regiospecific bromination. Here, w...
journal_title：Nature chemical biology
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更新日期：2021-01-01 00:00:00
