Researchers should reach beyond the science bubble p.391

doi: 10.1038/542391a

Pluto could be staging a comeback — and it’s not alone p.392

doi: 10.1038/542392b

Gene editing in legal limbo in Europe p.392

doi: 10.1038/542392a

Inside the Chinese lab poised to study world's most dangerous pathogens p.399

doi: 10.1038/nature.2017.21487

Broad Institute wins bitter battle over CRISPR patents p.401

doi: 10.1038/nature.2017.21502

Giant crack in Antarctic ice shelf spotlights advances in glaciology p.402

doi: 10.1038/nature.2017.21507

Delay in hiring science advisers intensifies Brexit worries p.403

doi: 10.1038/nature.2017.21511

Collapse of Aztec society linked to catastrophic salmonella outbreak p.404

doi: 10.1038/nature.2017.21485

The race to map the human body — one cell at a time p.404

doi: 10.1038/nature.2017.21508

An epigenetics gold rush: new controls for gene expression p.406

doi: 10.1038/542406a

Diversity in sight p.418

doi: 10.1038/nature21498

Predictable ice ages on a chaotic planet p.419

doi: 10.1038/542419a

RNA editing packs a one-two punch p.420

doi: 10.1038/542420a

Earth's seven sisters p.421

doi: 10.1038/542421a

Organic analogues of graphene p.423

doi: 10.1038/nature21503

A targeted treatment with off-target risks p.424

doi: 10.1038/nature21504

A simple rule to determine which insolation cycles lead to interglacials p.427

doi: 10.1038/nature21364

Prevalence and architecture of de novo mutations in developmental disorders p.433

doi: 10.1038/nature21062

Inhibition decorrelates visual feature representations in the inner retina p.439

doi: 10.1038/nature21394

Sterile protection against human malaria by chemoattenuated PfSPZ vaccine p.445

doi: 10.1038/nature21060

Adipose-derived circulating miRNAs regulate gene expression in other tissues p.450

doi: 10.1038/nature21365

Seven temperate terrestrial planets around the nearby ultracool dwarf star TRAPPIST-1 p.456

doi: 10.1038/nature21360

Static non-reciprocity in mechanical metamaterials p.461

doi: 10.1038/nature21044

Onset of the aerobic nitrogen cycle during the Great Oxidation Event p.465

doi: 10.1038/nature20826

Theory of chaotic orbital variations confirmed by Cretaceous geological evidence p.468

doi: 10.1038/nature21402

Ancestral morphology of crown-group molluscs revealed by a new Ordovician stem aculiferan p.471

doi: 10.1038/nature21055

m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition p.475

The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one-third of zebrafish maternal messenger RNAs (mRNAs) can be N6-methyladenosine (m6A) modified, and the clearance of these maternal mRNAs is facilitated by an m6A-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of m6A-modified maternal mRNAs and impedes zygotic genome activation. These embryos fail to initiate timely MZT, undergo cell-cycle pause, and remain developmentally delayed throughout larval life. Our study reveals m6A-dependent RNA decay as a previously unidentified maternally driven mechanism that regulates maternal mRNA clearance during zebrafish MZT, highlighting the critical role of m6A mRNA methylation in transcriptome switching and animal development.

doi: 10.1038/nature21355

Metabolic gatekeeper function of B-lymphoid transcription factors p.479

doi: 10.1038/nature21076

Synthetic essentiality of chromatin remodelling factor CHD1 in PTEN-deficient cancer p.484

doi: 10.1038/nature21357

Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells p.489

Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation. The phosphatidylinositol 3-kinase δ (PI3Kδ) pathway regulates AID by suppressing its expression in B cells. Drugs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kδ activity directly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B cells. Here we show that treatment of primary mouse B cells with idelalisib or duvelisib, and to a lesser extent ibrutinib, enhanced the expression of AID and increased somatic hypermutation and chromosomal translocation frequency to the Igh locus and to several AID off-target sites. Both of these effects were completely abrogated in AID-deficient B cells. PI3Kδ inhibitors or ibrutinib increased the formation of AID-dependent tumours in pristane-treated mice. Consistently, PI3Kδ inhibitors enhanced AID expression and translocation frequency to IGH and AID off-target sites in human chronic lymphocytic leukaemia and mantle cell lymphoma cell lines, and patients treated with idelalisib, but not ibrutinib, showed increased somatic hypermutation in AID off-targets. In summary, we show that PI3Kδ or Bruton’s tyrosine kinase inhibitors increase genomic instability in normal and neoplastic B cells by an AID-dependent mechanism. This effect should be carefully considered, as such inhibitors can be administered to patients for years.

doi: 10.1038/nature21406

Editing and methylation at a single site by functionally interdependent activities p.494

doi: 10.1038/nature21396

Basis of catalytic assembly of the mitotic checkpoint complex p.498

doi: 10.1038/nature21384