HIV-1 Env transitions from a closed to an open state upon binding to its cellular receptor. Single-particle cryo-EM analysis now reveals the closed state of the HIV-1 Env trimer at ~6-å resolution, featuring three gp41 helices at the center of the trimer depicted here by the tri-fold organization of the snowdrop's sepals. These findings indicate that HIV-1 enters the cell via mechanisms similar to influenza and other viruses. Image from Elena Moiseeva / Alamy. pp 1352–1357

The Cancer Genome Atlas (TCGA) Research Network has profiled a large number of different human tumors. Jacobsen and colleagues analyze data from >3,000 tumors across 11 cancer types to generate a pan-cancer network of 143 recurrent miRNA–target mRNA relationships. These relationships can also be explored online at http://cancerminer.org. Other TCGA papers can be explored in a special focus (http://www.nature.com/tcga/). Illustration from Ikon Images / Alamy. pp 1325–1332

The heterohexameric AAA+ complex of the eukaryotic 26S proteasome unfolds substrates prior to degradation. Martin and colleagues reconstitute proteasomes with recombinant subunits of the yeast unfoldase (Rpt1–6) to reveal distinct roles of each subunit in substrate processing, peptidase binding and gate opening. Image from Alamy / © Andrew Paterson. pp 1164–1172

How plant pri-miRNAs with complex secondary structures are recognized and processed has been unclear. Zhang and colleagues now suggest that, unlike canonical processing of pri-miRNAs, terminal-loop-branched pri-miRNAs can be processed by Dicer-like1 (DCL1) complexes bidirectionally. Original image from itanistock / Alamy, adapted by Erin Dewalt. pp 1106–1115

mRNA localization provides spatial and temporal control of protein expression. Using single-molecule reconstitutions, Trybus and colleagues reveal the mechanism of class V myosinmediated mRNA transport, showing how multiple mRNA "zip codes" synergize to assemble a processive complex and enhance transport on actin cables. Original image from Redmond Durrell / Alamy, adapted by Erin Dewalt. pp 952–957

The DNA helicase RECQL5 represses transcription by direct interaction with RNA polymerase II (Pol II). A cryo-EM reconstruction by Nogales and colleagues now shows elongating Pol II stalled by RECQL5, with RECQL5 and the polymerase facing each other on DNA with opposing directionalities. pp 892–899

Prp8, a key protein component of the spliceosome, is implicated in both steps of pre-mRNA splicing. MacMillan and colleagues now uncover the structural rearrangement of the Prp8 RNase H domain from a closed to an open conformation that creates a binding site for a metal ion required for the second splicing reaction. Image from Tips Images/Tips Italia Srl a socio unico/Alamy. pp 728–734

During early development, one of the two female X chromosomes forms a compact, silent nuclear compartment. Obuse and colleagues now provide new insights into the condensation mechanisms. Artwork by Yuka Naraki shows two calico cats, whose tortoiseshell-like color is a typical phenotype of X inactivation, representing compact inactive and decondensed active X. pp 566–573

The function of nuclear actin remains poorly understood. Shen and colleagues investigate the yeast actin-containing INO80 chromatin remodeling complex, and revealed that monomeric actin contributes to INO80 remodeling activity, suggesting that nuclear actin uses a fundamentally different mechanism from cytoplasmic actin. Image from Thinkstock. pp 426–432

In this issue, we feature a special Focus on Epigenetic Dynamics (http://www.nature.com/nsmb/focus/epigeneticdynamics/), comprising specially commissioned Reviews that discuss the dynamic nature of histone modifications, DNA methylation, chromatin organization and other epigenetic features of genomes and their functional significance. Cover design by Erin Dewalt. pp 259–308

To initiate transcription, Escherichia coli RNA polymerase must locate promoter sequences, which comprise <2% of the bacterial genome. By visualizing RNA polymerase in real time as it searches for promoters and determining single-molecule target association rates, Greene and colleagues demonstrate that promoter search is dominated by three dimensional diffusion in vitro. Image by Wilm Ihlenfeld from iStockphoto. pp 174–181

During the life cycle of dengue virus, two viral membrane proteins, E and M, undergo dramatic structural changes. The cryo-EM structure of the mature prefusion dengue virion reveals the detailed interactions between E and M, providing insight into how conformational changes are triggered. Cover art by Erin Dewalt, based on an image from Hong Zhou and colleagues. pp 105–110