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  • This issue of Nature Structural & Molecular Biology presents studies investigating RNA processing, including mechanisms of splicing, biogenesis of the splicing machinery, decoding of mRNA by the ribosome, and deadenylation of mRNA for degradation. We are also delighted to be publishing News & Views and Comment pieces that reflect on these exciting advances in the field.

  • NAD(H) redox homeostasis has a fundamental role in cellular metabolism. We screened for potential modulators of NAD(H) using a genome-scale RNA interference (RNAi) approach combined with SoNar, a high-performance sensor that is sensitive to the redox state of NAD(H). Our analysis identified HES4 as a negative regulator of the NADH/NAD+ ratio that influences pyrimidine biosynthesis and exerts a potent oncogenic effect.

    Research Briefing
  • Here the authors used cryogenic electron microscopy and biochemistry to understand how yeast Mcm10 exerts its essential role in DNA replication initiation, finding that it splits the double Cdc45-MCM-GINS-Polε structure. The lagging-strand template is ejected from each MCM ring as the central channel of the helicase becomes too tight to accommodate two DNA strands.

    • Sarah S. Henrikus
    • Marta H. Gross
    • Alessandro Costa
    ArticleOpen Access
  • Since Nature Structural and Molecular Biology was started 30 years ago, our understanding of transcription and mRNA processing has been revolutionized through structural and mechanistic studies. Here, we present our personal views of the advances in understanding the production of mature eukaryotic mRNAs over the past decade.

    • Lori A. Passmore
    • Suyang Zhang
  • Branch point selection is required for pre-mRNA splicing, and its mis-regulation is associated with many diseases. Two structural studies provide insights into the dynamics of active site formation and the spliceosomal proteins that may contribute to activation of the correct branch point in eukaryotic introns.

    • Sara R. Downs
    • Bec Grace
    • Jeffrey A. Pleiss
    News & Views
  • Targeted biologics delivery requires programming multicomponent protein nanomaterials to enable selective targeting and response to environment changes in a single unified framework. A novel protein nanoparticle platform has been designed to modulate cell-surface target specificity, cargo packaging, and pH-dependent release of encapsulated cargo, providing exciting possibilities in biologics delivery.

    Research Briefing
  • Designed novel protein nanoparticle technology integrates antibody targeting and responds to changes in environmental conditions to release protected molecular cargoes, opening new applications for precision medicine.

    • Erin C. Yang
    • Robby Divine
    • David Baker
    ArticleOpen Access
  • Stabilization of a branch structure would intuitively suggest a direct connection between trunk and bough, but in actin filament networks, cortactin clamps the branching Arp2/3 complex to the daughter filament. This has fundamental consequences for mechanistic understanding of actin branch turnover and cortactin biology.

    • Klemens Rottner
    • Peter Bieling
    News & Views
  • ADP-ribosylation regulates the activity of numerous proteins involved in the DNA damage response and repair. A new study shows that telomeric DNA can be ADP-ribosylated by PARP1, and prompt removal of the ADP-ribose by TARG1 is essential to preserve telomere integrity, unveiling DNA–ADP-ribosylation as a novel player in telomere stability.

    • Ylli Doksani
    • Francisca Lottersberger
    News & Views
  • Telomeres are endogenous cellular targets of DNA ADP-ribosylation (DNA-ADPr). TARG1-regulated DNA-ADPr is coupled to lagging telomere DNA strand synthesis, and persistent DNA-ADPr, due to TARG1 deficiency, leads to telomere shortening and fragility.

    • Anne R. Wondisford
    • Junyeop Lee
    • Roderick J. O’Sullivan
    ArticleOpen Access
  • The authors uncovered an antiparasitic molecule that exhibits broad-spectrum activity against parasitic flukes through engagement of a recently discovered transient receptor potential ion channel.

    • Daniel J. Sprague
    • Sang-Kyu Park
    • Jonathan S. Marchant
  • Systemic RNA interference (RNAi) in Caenorhabditis elegans is initiated by SID-1-mediated double-stranded RNA (dsRNA) internalization. By combining cryo-electron microscopy (cryo-EM), in vitro and in vivo assays, we show how SID-1 specifically recognizes dsRNA and provide important insights into dsRNA internalization by SID-1.

    Research Briefing