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Featured Articles

Featured Articles highlight the best papers published in NAR. These articles are chosen by the Executive Editors on the recommendation of Editorial Board Members and Referees. They represent the top 5% of papers in terms of originality, significance and scientific excellence. The articles are accompanied by a brief synopsis explaining the findings of the paper and where they fit in the broader context of nucleic acids research.

Recently Added Featured Articles

RNPC1 modulates the RNA-binding activity of, and cooperates with, HuR to regulate p21 mRNA stability
P21, a cyclin-dependent kinase inhibitor, is necessary for proper cell cycle progression. Previous studies showed that p21 expression is regulated through p21 mRNA stability by RNPC1, a target of the p53 family, and HuR, a member of the ELAV family RNA-binding proteins. In this article, the authors demonstrate that RNPC1 and HuR physically interact through their RNA recognition motifs and that RNPC1 and HuR, both of which can bind AU-rich elements in p21 3’UTR, preferentially bind the upstream and downstream AU-rich elements, respectively. In addition, the authors show that the RNA-binding activity of HuR to p21 transcript was enhanced by RNPC1 in vitro and in vivo and that the ability of RNPC1 to regulate p21 mRNA stability is dependent on HuR. Together, the authors hypothesize that RNPC1 modulates the RNA-binding activity of, and cooperates with, HuR to regulate p21 mRNA stability.
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The ribosome assembly factor Nep1 responsible for Bowen–Conradi syndrome is a pseudouridine-N1-specific methyltransferase
Ribosome biogenesis in eukaryotic cells is a complicated multi-stage process and requires the action of a plethora of different ‘helper’ proteins such as Nep1. The absence of Nep1 leads to defects in the processing of the RNA component of the small ribosomal subunit. In humans, a mutation of Nep1 is the cause for Bowen-Conradi syndrome – a fatal developmental disorder. In this article, Nep1 is identified as an enzyme that transfers a methyl group to the N1-nitrogen of a pseudouridine nucleotide in RNAs. Nep1 is the first protein with this specific enzymatic activity. Interestingly, the RNA-binding site of Nep1 identified by NMR includes the amino acid mutated in Bowen-Conradi syndrome.
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Yeast arginine methyltransferase Hmt1p regulates transcription elongation and termination by methylating Npl3p
This manuscript makes a valuable contribution to the understanding of how the RNA binding protein Npl3p affects transcription elongation and termination in budding yeast through its regulation by the arginine methyltransferse Hmt1p.
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Riboswitch structure: an internal residue mimicking the purine ligand
Riboswitches are recently discovered structured elements that regulate gene expression by binding to small metabolites. Their study is of great interest from a number of different aspects, such as improving our understanding of RNA structure and folding. This article describes the three-dimensional structure of a purine riboswitch aptamer mutant that has been excluded through evolution. What is particularly interesting with the structure of this mutant is that it mimics the structure of the purine-bound wild-type aptamer, but does so in the absence of ligand. The structure clearly explains why this mutant is impaired for ligand binding and why it has been excluded through evolution. In addition, it provides valuable insights into the folding pathway of purine riboswitches and opens new avenues for the design of antibiotics that block ligand-dependent folding of riboswitches. This manuscript highlights an important aspect of sequence conservation through evolution and provides a novel example of structural mimicry. Read on

Mining regulatory 5'UTRs from cDNA deep sequencing datasets
Bacteria must continuously regulate gene expression in reaction to diverse environmental stimuli and growth conditions. In many cases this regulation is mediated by RNA motifs known as regulatory 5’UTRs (r5’UTRs) found upstream of protein-encoding sequences of messenger RNAs. Several recent studies have suggested that the number and diversity of bacterial r5’UTRs has been significantly underestimated. New high-throughput sequencing (HTS) techniques could provide powerful tools for the discovery of novel r5’UTRs; however, the size and complexity of the datasets generated by these technologies makes it difficult to differentiate r5’UTRs from the multitude of other types of RNAs detected. Here, the authors developed and implemented a computational approach to identify r5’UTRs from within large datasets of RNAs recently identified by HTS in Vibrio cholerae, the causative agent of the diarrheal disease cholera. Read on

An intermolecular RNA triplex provides insight into structural determinants for the pseudoknot stimulator of –1 ribosomal frameshifting
-1 programmed ribosomal frameshifting (PRF) is used by a variety of viruses, including HIV and SARS corona virus to switch the reading-frame during translation for viral protein synthesis. The efficiency of -1 PRF in eukaryotic systems can be dramatically enhanced by an mRNA embedded stimulator which is usually an RNA pseudoknot structure. Using a pseudoknot derived from human telomerase RNA, which also possesses a specific tertiary interaction named base-triple, this article demonstrates that the -1 PRF efficiency of this pseudoknot is reduced to the background level without its base-triples. More importantly, reconstitution of these base-triples by a bimolecular approach reveals that they are essential for -1 PRF. Finally, it suggests that -1 PRF, induced by an in-trans RNA via specific base-triple interactions with particular mRNAs, could be a plausible regulatory function for non-coding RNAs. Read on

Crystal structure of Pyrococcus horikoshii tryptophanyl-tRNA synthetase and structure-based phylogenetic analysis suggest an archaeal origin of tryptophanyl-tRNA synthetase
This article presents the first crystal structure of an archaeal TrpRS, Pyrococcus horikoshii TrpRS, in complex with TrpAMP. With this structure the authors performed a structure-based phylogenetic study of TrpRS and TyrRS which, for the first time, includes representatives from all three domains of life. The results imply that TrpRS originated from archaeal TyrRS and suggest that the emergence of TrpRS and subsequent acquisition by bacteria genre occurred at early stages of evolution. This work provides new insights into the evolution of TrpRS and TyrRS. Read on

Sequence–structure relationships in RNA loops: establishing the basis for loop homology modeling
Base-paired segments in RNA molecules fold into regular helical structures, while unpaired segments (loops) are seemingly unstructured. However, loops adopt a wide range of structural motifs, impart structural flexibility, and can therefore be seen as the actual source of not only the structural, but also the functional diversity of RNA molecules influencing the binding of small molecules, proteins, or other nucleic acids. Hence, loops are important carriers of RNA function. This article reports results from a systematic survey of experimentally determined RNA loop structures and establishes the basis for the application of homology modeling to RNA loops. By exploring sequence-structure relationships, the level of sequence divergence was identified above which two RNA loops are less likely to adopt similar structures. Thus, a critical guiding threshold for homology-based modeling efforts was identified. The article introduces a web database application for RNA loop homology modeling. Read on

Two distinct regions in Staphylococcus aureus GatCAB guarantee accurate tRNA recognition
Aminoacyl-tRNA is the essential substrate for protein synthesis mostly made by direct acylation of the tRNA with the correct amino acid. However, many organisms and organelles form the amide aminoacyl-tRNAs, Gln-tRNAGln and Asn-tRNAAsn, by amidation of misacylated Glu-tRNAGln or Asp-tRNAAsn to the correct aminoacyl-tRNA catalyzed by a tRNA-dependent amidotransferase. This biosynthetic route of aminoacyl-tRNA synthesis is believed to precede evolutionarily the direct acylation by aminoacyl-tRNA synthetases. Structural and biochemical studies with the heterotrimeric Staphylococcus aureus GatCAB amidotransferase reveal two protein domains that interact with tRNA to ensure correct amide aminoacyl-tRNA formation.
(i) The tail domain of the amidotransferase specifically recognizes D-loop and the variable loop of the tRNA. (ii) A 310 turn structural motif in the catalytic domain provides specific recognition of the tRNA’s U1-A72 base allowing for discrimination of tRNAGln and tRNAAsn from tRNAGlu and tRNAAsp. Read on

Previous Featured Articles

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