Reviews & Analysis

Three recent reports explore how PRDM9 binds to meiotic hotspots within the genome and provide compelling evidence that hotspot erosion leads to speciation.

During assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs), the RNA-binding protein (RBP) Gemin5 recognizes the snRNP code and interacts with the large Gemin2–SMN complex. So et al. now find that Gemin2 also interacts with U1-70K, thereby conferring a preferential advantage on U1 snRNP assembly, and they extrapolate that SMN–Gemin2 serves a general ribonucleoprotein-exchange function.

50 years ago, Jardetzky proposed the alternating-access model, which has shaped the theoretical understanding of how substrates are carried across cell membranes. Two studies now demonstrate that transporters from distinct families undergo unexpectedly large elevator-like movements and also suggest that an 'elevate and twist' mechanism is a common means of achieving alternating access across the membrane.

Unraveling the molecular arms race between virus and host has been taken to a new level. A cryo-EM study reveals in unprecedented detail how the herpesvirus immune-evasion protein ICP47 inhibits the peptide transporter TAP.

Two structural studies provide new insights into the mechanisms regulating the DNA binding and activation of human HSF family members.

This Perspective highlights recent progress on the location, functions and mechanisms of N⁶-methyladenosine (m⁶A), the most abundant internal modification in eukaryotic mRNA. In particular, the authors discuss how m⁶A modification affects the mammalian RNA life cycle at multiple stages.

In this Review, the authors discuss emerging mechanisms of how the replication machinery of mammalian cells overcomes replication-fork obstacles, thus ensuring faithful genome duplication.

Release of neurotransmitters occurs by opening of a fusion pore in a manner thought to be mediated by SNARE proteins, but whether the fusion pore is a lipidic or a proteinaceous structure is controversial. A new study using very small nanodiscs shows that it is both.

Rea1 is an ATPase related to dynein motor proteins that has been implicated in the biogenesis of the 60S ribosomal subunit. A new cryo-EM study vividly demonstrates the power of structural methods, deciphering the role of Rea1 in monitoring key pre-60S maturation steps before the acquisition of export competence in budding yeast.

A comprehensive review of the discovery and molecular dissection of the eukaryotic ribosome-associated quality-control pathway for degradation of nascent proteins arising from interrupted translation.