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Pore-loop paddles in ClpX have an optimal size to generate the power stroke that translocates substrates through the central pore. Cover art by Erin Dewalt based on an image by ne2pi/ iStock / Getty Images Plus (p 974)
During protein synthesis, the growing nascent polypeptide chain acts as a positive or negative regulator of the rate of peptide-bond formation and ribosomal fidelity, and influences the efficiency of downstream protein-folding and targeting events. At a recent international meeting held on the banks of Lake Kawaguchi in Japan, scientists and students investigating diverse aspects of nascent-chain biology met to discuss their latest findings in the scenic presence of Mount Fuji.
A conserved long noncoding RNA expressed at the 5S rDNA ribosomal locus has acquired a novel function in alternative-splicing regulation in primates, owing to the insertion of a mobile Alu element. This discovery opens new perspectives regarding the roles of transposable elements in expanding the human transcriptome and may be applied as a biotechnology tool to drive gene-specific changes in alternative splicing.
The degradation of mRNAs involves removal of the 5′ protective cap via a decapping-enzyme complex, in a largely irreversible process that commits the transcript for destruction. Understanding how the decapping reaction is catalyzed and regulated are major goals in the field. New data suggest how the chemistry of decapping is controlled and orchestrated within the cell.
Drosophila Skywalker regulates the GTPase Rab35, thereby controlling the turnover of synaptic-vesicle proteins. A new crystal structure of the TBC domain of Skywalker reveals an unexpected phosphoinositide-binding pocket, which is critical for synaptic function and is disrupted in DOORS syndrome–causing mutations in the human Skywalker homolog TBC1D24.
Perinuclear localization of CED-3 zymogen in C. elegans germ cells and interaction with nuclear-pore protein NPP-14 inhibit autocatalytic activation of CED-3, a central event in apoptosis.
Structural, biochemical and functional analyses elucidate the mechanisms by which mutations in the TBC1D24 gene interfere with protein function, thus causing early-onset epilepsy and DOORS syndrome.
Single-molecule spectroscopy reveals the complete mechanochemical cycle of the AAA+ protease ClpXP: ADP release and ATP binding occur during the dwell phase, whereas ATP hydrolysis and Pi release occur during the burst phase.
The crystal structure of the Kluyveromyces lactis decapping enzyme complex Dcp1–Dcp2 is solved in the presence of activator Edc3 and reaction product m7GDP, revealing an active conformation of the enzyme.
The structure of the S. pombe Dcp2–Dcp1 decapping enzyme complex with human activator PNRC2 and tight-binding cap analog reveals a new conformation and, along with kinetics analyses, provides insight into substrate recognition and mechanisms of activators.
The E4 ligase UFD-2 is required for apoptosis induced by DNA damage in C. elegans, and for the resolution of RAD-51 foci during homologous recombination-dependent repair, thus coordinating these two cellular processes.
Structural and cross-linking analyses provide deeper insight into Zuo1's dual interactions with the ribosomal 60S and 40S subunits and indicate how Zuo1 may coordinate cotranslational protein folding and translation.
A primate-specific insertion of an Alu element in 5S-OT, a lncRNA transcribed from 5S rRNA loci, allows 5S-OT to regulate alternative splicing via RNA-RNA pairing and recruitment of the splicing factor U2AF65.
Analyses of Hsp90 mutants show no correlation between the speed of ATP turnover and chaperone activity in vivo, indicating that timing of conformational transitions, rather than cycle speed, is essential for Hsp90 function.
