Volume 548 Number 7667

Editorials

News

News Features

News & Views

Origins of Atlantic decadal swings p.284

Temperature variability in the North Atlantic Ocean is the result of many competing physical processes, but the relative roles of these processes is a source of contention. Here, scientists present two perspectives on the debate.

doi: 10.1038/nature23538

A bitter–sweet symphony p.285

Information about taste sensations, such as bitter or sweet, is relayed from the mouse tongue to the brain through taste-specific pathways. It emerges that semaphorin proteins guide the wiring of these pathways. See Letter p.330

doi: 10.1038/nature23537

Human metastases under scrutiny p.287

Sequences of the DNA and RNA of 500 human cancers that have spread from their primary site in the body take us a step closer to the convergence of basic science and patient benefit. See Article p.297

doi: 10.1038/nature23535

A turbulent stellar atmosphere in full view p.288

The dynamic motion of gas in the outer atmosphere of a red supergiant star has been mapped, providing clues to the mysterious mechanism that causes massive stars to lose mass through stellar winds. See Letter p.310

doi: 10.1038/548288a

Healthy skin rejects cancer p.289

Live imaging shows that healthy skin cells surround and expel neighbours that have cancer-promoting mutations, revealing that tissues can recognize and eliminate mutant cells to prevent tumour initiation. See Letter p.334

doi: 10.1038/nature23534

Articles

New gliding mammaliaforms from the Jurassic p.291

Maiopatagium, a haramiyid from the Jurassic Tiaojishan Formation (around 160 million years ago) of China was specialised for gliding with a patagium (wing membrane) and a fused wishbone, reminiscent of that of birds.

doi: 10.1038/nature23476

Letters

Rewiring the taste system p.330

Taste-receptor cells use distinct semaphorins to guide wiring of the peripheral taste system; targeted ectopic expression of SEMA3A or SEMA7A leads to bitter neurons responding to sweet tastes or sweet neurons responding to bitter tastes.

doi: 10.1038/nature23299

m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways p.338

N6-methyladenosine (m6A) is the most common and abundant messenger RNA modification, modulated by ‘writers’, ‘erasers’ and ‘readers’ of this mark. In vitro data have shown that m6A influences all fundamental aspects of mRNA metabolism, mainly mRNA stability, to determine stem cell fates. However, its in vivo physiological function in mammals and adult mammalian cells is still unknown. Here we show that the deletion of m6A ‘writer’ protein METTL3 in mouse T cells disrupts T cell homeostasis and differentiation. In a lymphopaenic mouse adoptive transfer model, naive Mettl3-deficient T cells failed to undergo homeostatic expansion and remained in the naive state for up to 12 weeks, thereby preventing colitis. Consistent with these observations, the mRNAs of SOCS family genes encoding the STAT signalling inhibitory proteins SOCS1, SOCS3 and CISH were marked by m6A, exhibited slower mRNA decay and showed increased mRNAs and levels of protein expression in Mettl3-deficient naive T cells. This increased SOCS family activity consequently inhibited IL-7-mediated STAT5 activation and T cell homeostatic proliferation and differentiation. We also found that m6A has important roles for inducible degradation of Socs mRNAs in response to IL-7 signalling in order to reprogram naive T cells for proliferation and differentiation. Our study elucidates for the first time, to our knowledge, the in vivo biological role of m6A modification in T-cell-mediated pathogenesis and reveals a novel mechanism of T cell homeostasis and signal-dependent induction of mRNA degradation.

doi: 10.1038/nature23450

mRNA 3′ uridylation and poly(A) tail length sculpt the mammalian maternal transcriptome p.347

A fundamental principle in biology is that the program for early development is established during oogenesis in the form of the maternal transcriptome. How the maternal transcriptome acquires the appropriate content and dosage of transcripts is not fully understood. Here we show that 3′ terminal uridylation of mRNA mediated by TUT4 and TUT7 sculpts the mouse maternal transcriptome by eliminating transcripts during oocyte growth. Uridylation mediated by TUT4 and TUT7 is essential for both oocyte maturation and fertility. In comparison to somatic cells, the oocyte transcriptome has a shorter poly(A) tail and a higher relative proportion of terminal oligo-uridylation. Deletion of TUT4 and TUT7 leads to the accumulation of a cohort of transcripts with a high frequency of very short poly(A) tails, and a loss of 3′ oligo-uridylation. By contrast, deficiency of TUT4 and TUT7 does not alter gene expression in a variety of somatic cells. In summary, we show that poly(A) tail length and 3′ terminal uridylation have essential and specific functions in shaping a functional maternal transcriptome.

doi: 10.1038/nature23318