NAR’s 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.
Translational control through programmed ribosomal frameshifting (PRF) is exploited widely by viruses and increasingly documented in cellular genes. The –2/–1 PRF signal of the arterivirus PRRSV uniquely lacks a frameshift-stimulatory RNA structure and requires a viral protein, nsp1β, for function. Here, the authors show that PRF is trans-activated by a complex of nsp1β and a cellular poly(C) binding protein (PCBP) which mimics the activity of a structured mRNA stimulator of PRF. This is the first description of a role for a trans-acting cellular protein in programmed frameshifting and the first evidence for a role for PCBPs in translational elongation.
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.
The STAR protein QKI-7 recruits PAPD4 to regulate post-transcriptional polyadenylation of target mRNAs
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.