Abstract:
:Regulation of gene expression by RNA processing mechanisms is now understood to be an important level of control in mammalian cells. Regulation at the level of RNA transcription, splicing, polyadenylation, nucleo-cytoplasmic transport, and translation into polypeptides has been well-studied. Alternative RNA processing events, such as alternative splicing, also have been recognized as key contributors to the complexity of mammalian gene expression. Pre-messenger RNAs (pre-mRNAs) may be polyadenylated in several different ways due to more than one polyadenylation signal, allowing a single gene to encode multiple mRNA transcripts. However, alternative polyadenylation has only recently taken the field as a major player in gene regulation. This review summarizes what is currently known about alternative polyadenylation. It covers results from bioinformatics, as well as those from investigations of viral and tissue-specific studies and, importantly, will set the stage for what is yet to come.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Lutz CSdoi
10.1021/cb800138wsubject
Has Abstractpub_date
2008-10-17 00:00:00pages
609-17issue
10eissn
1554-8929issn
1554-8937journal_volume
3pub_type
杂志文章,评审abstract::Nephronectin is an extracellular matrix protein that interacts with the α8β1 integrin receptor and plays a role in tissue and organ development, though the motifs that mediate adhesion to the receptor remain unclear. This paper describes the use of self-assembled monolayers to study the adhesion of α8β1-presenting cel...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb200186j
更新日期:2011-10-21 00:00:00
abstract::Ubiquitin specific protease 7 (USP7) regulates the protein stability of key cellular regulators in pathways ranging from apoptosis to neuronal development, making it a promising therapeutic target. Here we used an engineered, activated variant of the USP7 catalytic domain to perform structure-activity studies of elect...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00031
更新日期:2020-06-19 00:00:00
abstract::There is a pressing need for new molecular tools to target protein surfaces with high affinity and specificity. Here, we describe cyclic messenger RNA display with a trillion-member covalent peptide macrocycle library. Using this library, we have designed a number of high-affinity, redox-insensitive, cyclic peptides t...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb7001126
更新日期:2007-09-21 00:00:00
abstract::Glycosylphosphatidylinositol (GPI)-anchored proteins are abundant in the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness in humans and the related disease Nagana in cattle, and disruption of GPI biosynthesis is genetically and chemically validated as a drug target. Here, we exam...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb800143w
更新日期:2008-10-17 00:00:00
abstract::Cell-penetrating peptides (CPPs) are capable of delivering membrane-impermeable cargoes (including small molecules, peptides, proteins, nucleic acids, and nanoparticles) into the cytosol of mammalian cells and have the potential to revolutionize biomedical research and drug discovery. However, the mechanism of action ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00478
更新日期:2020-09-18 00:00:00
abstract::Hypoxia induces a complex circuit of gene expression that drives tumor progression and increases drug resistance. Defining these changes allows for an understanding of how hypoxia alters tumor biology and informs design of lead therapeutics. We probed the role of microRNA-544 (miR-544), which silences mammalian target...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.5b00265
更新日期:2015-10-16 00:00:00
abstract::RUVBL1 and RUVBL2 are ATPases associated with diverse cellular activities (AAAs) that form a complex involved in a variety of cellular processes, including chromatin remodeling and regulation of gene expression. RUVBLs have a strong link to oncogenesis, where overexpression is correlated with tumor growth and poor pro...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b00904
更新日期:2019-02-15 00:00:00
abstract::Protein-fragment complementation assays (PCAs) are widely used for investigating protein interactions. However, the fragments used are structurally compromised and have not been optimized nor thoroughly characterized for accurately assessing these interactions. We took advantage of the small size and bright luminescen...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.5b00753
更新日期:2016-02-19 00:00:00
abstract::Alzheimer's Disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The current treatment options for AD are limited to ameliorating cognitive decline temporarily and not reversing or preventing the progression of dementia. Hence, more effective therapeutic strategies are needed ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00851
更新日期:2020-12-18 00:00:00
abstract::Cocaine esterase (CocE) is known as the most efficient natural enzyme for cocaine hydrolysis. The major obstacle to the clinical application of wild-type CocE is the thermoinstability with a half-life of only ∼12 min at 37 °C. The previously designed T172R/G173Q mutant (denoted as enzyme E172-173) with an improved in ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb500257s
更新日期:2014-08-15 00:00:00
abstract::The neurotoxin saxitoxin and related paralytic shellfish toxins are produced by multiple species of cyanobacteria and dinoflagellates. This study investigates the two saxitoxin-producing strains of Scytonema crispum, CAWBG524 and CAWBG72, isolated in New Zealand. Each strain was previously reported to have a distinct ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b00608
更新日期:2018-11-16 00:00:00
abstract::Aminoglycoside antibiotics were among the first antibiotics discovered and used clinically. Although they have never completely fallen out of favor, their importance has waned due to the emergence of other broad-spectrum antibiotics with fewer side effects. Today, with the dramatically increasing rate of infections ca...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb3005116
更新日期:2013-01-18 00:00:00
abstract::The goal of incorporating renewable carbon into the fuel and chemical enterprise will most likely be successful when combined systems of biocatalysts and chemical catalysts are exploited. Significant efforts in the biocatalytic release of sugars from biomass are being pursued for subsequent use in fermentation. Two re...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb7001522
更新日期:2007-08-17 00:00:00
abstract::Tumor heterogeneity has hampered the development of novel effective therapeutic options for aggressive cancers, including the deadly primary adult brain tumor glioblastoma (GBM). Intratumoral heterogeneity is partially attributed to the tumor initiating cell (TIC) subset that contains highly tumorigenic, stem-like cel...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b00251
更新日期:2018-08-17 00:00:00
abstract::Available crystal structures of opioid receptors provide a high-resolution picture of ligand binding at the primary ("orthosteric") site, that is, the site targeted by endogenous ligands. Recently, positive allosteric modulators of opioid receptors have also been discovered, but their modes of binding and action remai...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.5b00712
更新日期:2016-05-20 00:00:00
abstract::The gibberellin (GA) phytohormones are produced not only by plants but also by fungi and bacteria. Previous characterization of a cytochrome P450 (CYP)-rich GA biosynthetic operon found in many symbiotic, nitrogen-fixing rhizobia led to the elucidation of bacterial GA biosynthesis and implicated GA9 as the final produ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b01038
更新日期:2017-04-21 00:00:00
abstract::Labeling of virus opens new pathways for the understanding of viruses themselves and facilitates the utilization of viruses in modern biology, medicine, and materials. Based on the characteristic that viruses hijack their host cellular machineries to survive and reproduce themselves, a host-cell-assisted strategy is p...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb2001878
更新日期:2012-04-20 00:00:00
abstract::The anxiolytic, anticonvulsant, muscle-relaxant, and sedative-hypnotic effects of benzodiazepine site ligands are mainly elicited by allosteric modulation of GABAA receptors via their extracellular αx+/γ2- ( x = 1, 2, 3, 5) interfaces. In addition, a low affinity binding site at the homologous α+/β- interfaces was rep...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b00145
更新日期:2018-08-17 00:00:00
abstract::Widespread use and misuse of antibiotics has allowed for the selection of resistant bacteria capable of avoiding the effects of antibiotics. The primary mechanism for resistance to aminoglycosides, a broad-spectrum class of antibiotics, is through covalent enzymatic modification of the drug, waning their bactericidal ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.5b01070
更新日期:2016-05-20 00:00:00
abstract::miRNAs are small non-coding RNAs that regulate about 60% of mammalian genes by modulating their transcript levels. Network scale studies of miRNA-mediated regulatory circuits demonstrate the central importance of this class of small RNA in the maintenance of biological robustness. More recently, several reports have d...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300650y
更新日期:2013-05-17 00:00:00
abstract::The quest for ever more selective kinase inhibitors as potential future drugs has yielded a large repertoire of chemical probes that are selective for specific kinase conformations. These probes have been useful tools to obtain structural snapshots of kinase conformational plasticity. Similarly, kinetic and thermodyna...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb500870a
更新日期:2015-01-16 00:00:00
abstract::The arabinosyltransferases responsible for the biosynthesis of the arabinan domains of two abundant heteropolysaccharides of the cell envelope of all mycobacterial species, lipoarabinomannan and arabinogalactan, are validated drug targets. Using a cell envelope preparation from Mycobacterium smegmatis as the enzyme so...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b00093
更新日期:2016-06-17 00:00:00
abstract::How primitive enzymes emerged from a primordial pool remains a fundamental unanswered question with important practical implications in synthetic biology. Here we show that a de novo evolved ATP binding protein, selected solely on the basis of its ability to bind ATP, mediates the regiospecific hydrolysis of ATP to AD...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb900109w
更新日期:2009-08-21 00:00:00
abstract::Next-generation DNA sequencing technologies have led to a massive accumulation of genomic and transcriptomic data from patients and healthy individuals. The major challenge ahead is to understand the functional significance of the elements of the human genome and transcriptome, and implications for diagnosis and treat...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/acschembio.7b00657
更新日期:2018-02-16 00:00:00
abstract::The number of bacterial strains that are resistant against antibiotics increased dramatically during the past decades. This fact stresses the urgent need for the development of new antibacterial agents with novel modes of action targeting essential enzymes such as RNA polymerase (RNAP). Bacterial RNAP is a large multi...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb3005758
更新日期:2013-04-19 00:00:00
abstract::Though phenotypic and target-based high-throughput screening approaches have been employed to discover new antibiotics, the identification of promising therapeutic candidates remains challenging. Each approach provides different information, and understanding their results can provide hypotheses for a mechanism of act...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00468
更新日期:2017-09-15 00:00:00
abstract::A major goal of personalized medicine in oncology is the identification of drugs with predictable efficacy based on a specific trait of the cancer cell, as has been demonstrated with gleevec (presence of Bcr-Abl protein), herceptin (Her2 overexpression), and iressa (presence of a specific EGFR mutation). This is a cha...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb4005832
更新日期:2013-10-18 00:00:00
abstract::Elevation of reactive oxygen species (ROS) levels has been observed in many cancer cells relative to nontransformed cells, and recent reports have suggested that small-molecule enhancers of ROS may selectively kill cancer cells in various in vitro and in vivo models. We used a high-throughput screening approach to ide...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300653v
更新日期:2013-05-17 00:00:00
abstract::Human glucosylcerebrosidase 2 (GBA2) of the CAZy family GH116 is responsible for the breakdown of glycosphingolipids on the cytoplasmic face of the endoplasmic reticulum and Golgi apparatus. Genetic defects in GBA2 result in spastic paraplegia and cerebellar ataxia, while cross-talk between GBA2 and GBA1 glucosylceram...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b00192
更新日期:2016-07-15 00:00:00
abstract::The canonical NF-κB signaling pathway is a mediator of the cellular inflammatory response and a target for developing therapeutics for multiple human diseases. The furthest downstream proteins in the pathway, the p50/p65 transcription factor heterodimer, have been recalcitrant toward small molecule inhibition despite ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b00751
更新日期:2017-01-20 00:00:00