During development, ribosome biogenesis and translation reach peak activities, due to impetuous cell proliferation. Current models predict that protein synthesis elevation is controlled by transcription factors and signalling pathways. Developmental models addressing translation factors overexpression effects are lacking. Eukaryotic Initiation Factor 6 (eIF6) is necessary for ribosome biogenesis and efficient translation. eIF6 is a single gene, conserved from yeasts to mammals, suggesting a tight regulation need. We generated a Drosophila melanogaster model of eIF6 upregulation, leading to a boost in general translation and the shut-down of the ecdysone biosynthetic pathway. Indeed, translation modulation in S2 cells showed that translational rate and ecdysone biosynthesis are inversely correlated. In vivo, eIF6-driven alterations delayed Programmed Cell Death (PCD), resulting in aberrant phenotypes, partially rescued by ecdysone administration. Our data show that eIF6 triggers a translation program with far-reaching effects on metabolism and development, stressing the driving and central role of translation.
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http://dx.doi.org/10.1016/j.ydbio.2019.05.013 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
C-Terminal cyclic imides are posttranslational modifications that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging-related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide susceptibility to C-terminal cyclic imide formation or their effect on protein stability have not been explored in detail.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry, Chemical Theory Center, University of Minnesota, Minneapolis, MN 55455-0431.
Multiconfiguration pair-density functional theory (MC-PDFT) was proposed a decade ago, but it is still in the early stage of density functional development. MC-PDFT uses functionals that are called on-top functionals; they depend on the density and the on-top pair density. Most MC-PDFT calculations to date have been unoptimized translations of generalized gradient approximations (GGAs) of Kohn-Sham density functional theory (KS-DFT).
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January 2025
Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016.
Posttranslational modifications (PTMs) of proteins play critical roles in regulating many cellular events. Antibodies targeting site-specific PTMs are essential tools for detecting and enriching PTMs at sites of interest. However, fundamental difficulties in molecular recognition of both PTM and surrounding peptide sequence have hindered the efficient generation of highly sequence-specific anti-PTM antibodies.
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January 2025
Computational Radiology Laboratory, Boston Children's Hospital, Boston, MA 02115.
This study presents the construction of a comprehensive spatiotemporal atlas of white matter tracts in the fetal brain for every gestational week between 23 and 36 wk using diffusion MRI (dMRI). Our research leverages data collected from fetal MRI scans, capturing the dynamic changes in the brain's architecture and microstructure during this critical period. The atlas includes 60 distinct white matter tracts, including commissural, projection, and association fibers.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210.
The homo-dodecameric ring-shaped RNA binding attenuation protein (TRAP) from binds up to twelve tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5' leader region of the operon mRNA, thereby downregulating biosynthesis of Trp. Thermodynamic measurements of Trp binding have revealed a range of cooperative behavior for different TRAP variants, even if the averaged apparent affinities for Trp have been found to be similar. Proximity between the ligand binding sites, and the ligand-coupled disorder-to-order transition has implicated nearest-neighbor interactions in cooperativity.
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