Molecular Cell is a Cell Press journal that aims to publish the best papers in molecular biology.
Molecular Cell
Online Now: Structure and engineering of the large serine recombinase Bxb1 for gene integration Online now:
Everything you always wanted to know about plasmid chromatinization … but were afraid to ask
RNAP at the apex: Cryo-ET unveils the torsional tango between plasmid DNA and double-helix-melting proteins
Use it or lose it: A ubiquitin-mediated autophagy pathway for degradation of MHC-I in pancreatic cancer
Mitochondria across the globe: Diverse voices, shared energy
Structural basis for RISC assembly of human Argonaute2
Uncovering the initial response: Intra-mitochondrial surveillance activates the UPRmt
Design principles of a membrane-spanning ubiquitin ligase
Chromatin architectures underlying plasmid-based assays for regulatory variant effects
A multi-subunit autophagic capture complex facilitates degradation of ER-stalled MHC class I in pancreatic cancer
Mallory et al. develop plasmid Fiber-seq to map chromatin architecture along individual transfected plasmids at near-nucleotide resolution, which reveals that plasmids adopt heterogeneous chromatin patterns that regulate transcriptional activity. Combined with high-throughput reporter assays, this approach distinguishes the molecular mechanisms by which non-coding variants alter regulatory element activity.
In this issue of Molecular Cell, Mallory et al. use single-molecule DNA methyltransferase footprinting to provide an unprecedented view of the chromatin and transcriptional state of reporter plasmid molecules in human cells.
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In this issue, Zhang and Cañari-Chumpitaz et al. find that RNA polymerase (RNAP) preferentially binds to the apices of supercoiled DNA plectonemes, which facilitates promoter escape but imposes a torsional trade-off during elongation. In the presence of torsional blocks, it generates twin supercoiling domains and drives cooperative transcription.
Williams et al. report structures of the MMM complex, a membrane-spanning E3 ligase. A single α helix suspends an activated RING domain below the plasma membrane to ubiquitylate the GPCR Smoothened and attenuate Hedgehog signaling. This work establishes a structural and mechanistic blueprint for how transmembrane E3s search and destroy key receptors in development, immunity, and metabolism.
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Like mitochondria themselves, research on this organelle can take many shapes and sizes. This month, to coincide with the Cell Press Symposia: Multifaceted Mitochondria, we are highlighting the diversity of the global mitochondria community with contributions from researchers at all career stages published across Cell Metabolism, Molecular Cell, Cell Reports, and Trends in Endocrinology and Metabolism. Together, these voices showcase the central role of mitochondrial research in metabolism, inflammation, cell biology, and much more.
Zhang et al. report cryo-EM structures of AGO2-siRNA complexes capturing RISC assembly intermediates. They reveal MID-PIWI-mediated duplex loading, α14-guided end sensing, and stepwise passenger peeling. Target RNAs drive passenger ejection, even after cleavage, which supports target-assisted passenger ejection and a bifunctional role of mRNAs in RNAi.
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In this issue of Molecular Cell, Berquez et al. reveal that MHC-I is degraded from within the endoplasmic reticulum (ER) by a ubiquitin-driven autophagy pathway involving co-operation of a cytoplasmic and an ER-phagy cargo receptor.
Taskin, Shankar, Peselj, et al. demonstrate that mitochondria possess an intrinsic surveillance system that senses mild oxidative stress and activates the UPRmt before damage signals reach the cytosol. By uncovering redox-sensitive proteases as early targets, they redefine how mitochondrial stress surveillance is initiated.
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Berquez et al. show that delayed ER exit of MHC class I in PDAC cells promotes its autophagic degradation via a TEX264-NBR1 complex. Impaired peptide loading increases MHC class I targeting to autophagosomes. A CRISPRi screen identifies the ER E3 ligase NFXL1, which promotes MHC class I ubiquitylation and autophagic capture.
Soma et al. present cryo-EM structures of the large serine recombinase Bxb1 bound to attP and attB substrates and provide mechanistic insights into attP/attB recognition, synaptic complex formation, and strand exchange via subunit rotation, enabling structure-guided engineering of Bxb1 variants with reprogrammed DNA preferences and enhanced recombination activity.
