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2016 Breakthrough Articles

breakthrough articles

Breakthrough Articles present high-impact studies answering long-standing questions in the field of nucleic acids research and/or opening up new areas and mechanistic hypotheses for investigation. These articles are chosen by the Editors on the recommendation of Editorial Board Members and Referees. 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. They represent the very best papers published at NAR.

Read the full editorial 'Breakthrough Articles: Putting science first'.

2015 Breakthrough Articles available here


gkw153Identification of a mismatch-specific endonuclease in hyperthermophilic Archaea

Ishino S, Nishi Y, Oda S, Uemori T, Sagara T, Takatsu N, Yamagami T, Shirai T, Ishino Y





It has been unclear whether Archaea has any mismatch repair system, because no study showing the functional MutS/MutL proteins in Archaea has been reported to date. Here the authors identified the novel endonuclease, which specifically cleaves double-stranded DNA containing a mismatch base pair to produce 5'-protruding forms with the mismatched base pair in the central position, from hyperthermophilic Archaea. This enzyme is conserved only in Archaea and small groups in bacteria. This discovery will open the door to elucidate the novel mismatch repair process in Archaea and some bacteria, which do not have the conventional MutS/MutL-dependent mismatch repair system.
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gkw118The STAR protein QKI-7 recruits PAPD4 to regulate post-transcriptional polyadenylation of target mRNAs

Yamagishi R, Tsusaka T, Mitsunaga H, Maehata T, Hoshino S





Using a pulse-chase strategy, the authors identify the STAR RNA binding protein QKI as a new player in cytoplasmic polyadenylation outside the germ line. Importantly, only one of the three alternatively spliced isoforms, QKI-7, stimulates elongation of poly(A) tails by recruiting the non-canonical poly(A) polymerase PAPD4/GLD2 to target mRNAs. Similar to the activation of maternal mRNAs in early development, QKI-7-mediated poly(A) tail lengthening enhances translation of critical target mRNAs including hnRNP-A1, the CDK inhibitor p27 and beta-catenin. In addition to expanding the repertoire of RNA-binding proteins that promote cytoplasmic polyadenylation and elucidating the underlying mechanism, the results of this study may aid in understanding the molecular basis of disease, as QKI has been implicated in the etiology of schizophrenia.
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gkw053Reversible acetylation on Lys501 regulates the activity of RNase II

Song L, Wang G, Malhotra A, Deutscher MP, Liang W






RNase II, a 3' to 5' processive exoribonuclease, is the major hydrolytic enzyme in Escherichia coli accounting for ∼90% of the total activity. Despite its importance, little is actually known about regulation of this enzyme. We show here that one residue, Lys501, is acetylated in RNase II. This modification, reversibly controlled by the acetyltransferase Pka, and the deacetylase CobB, affects binding of the substrate and thus decreases the catalytic activity of RNase II. As a consequence, the steady-state level of target RNAs of RNase II may be altered in the cells. We also find that under conditions of slowed growth, the acetylation level of RNase II is elevated and the activity of RNase II decreases, emphasizing the importance of this regulatory process. These findings indicate that acetylation can regulate the activity of a bacterial ribonuclease.
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gkv1068DIDA: A curated and annotated digenic diseases database

Gazzo AM, Daneels D, Cilia E, Bonduelle M, Abramowicz M, Van Dooren S, Smits G, Lenaerts T.





DIDA (DIgenic diseases DAtabase) is a novel database that provides for the first time detailed information on genes and associated genetic variants involved in digenic diseases, the simplest form of oligogenic inheritance. The web interface provides browsing and search functionalities, as well as documentation and help pages, general database statistics and references to the original publications from which the data have been collected. The possibility to submit novel digenic data to DIDA is also provided. Genes, variants, diseases and digenic combinations in DIDA are annotated with manually curated information and information mined from other online resources. Next to providing a unique resource for the development of new analysis methods, DIDA gives clinical and molecular geneticists a tool to find the most comprehensive information on the digenic nature of their diseases of interest.
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gkv1106dbMAE: the database of autosomal monoallelic expression

Savova V, Patsenker J, Vigneau S, Gimelbrant AA.





Recently, data on ‘random’ autosomal monoallelic expression has become available for the entire genome in multiple human and mouse tissues and cell types, creating a need for better access and dissemination. The database of autosomal monoallelic expression (dbMAE; https://mae.hms.harvard.edu) incorporates data from multiple recent reports of genome-wide analyses, including transcriptome-wide analyses of allelic imbalance in clonal cell populations based on sequence polymorphisms, as well as indirect identification, based on a specific chromatin signature present in MAE gene bodies. All source references, including raw data, are clearly described and hyperlinked. This ensures the utility of the resource as an initial screening tool for those interested in investigating the role of monoallelic expression in their specific genes and tissues of interest.
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