In the November 18 issue of Cell, discover an unidentified function for the eIF3 translation initiation factor as a scaffold for the dynamic associations of many preinitiation complex components, including the growth-regulating kinases mTOR and S6K1.
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Structural insights into distinct mechanisms of RNA polymerase II and III recruitment to snRNA promoters.
Nat Commun
January 2025
Human Technopole, Milan, Italy.
RNA polymerase III (Pol III) transcribes short, essential RNAs, including the U6 small nuclear RNA (snRNA). At U6 snRNA genes, Pol III is recruited by the snRNA Activating Protein Complex (SNAPc) and a Brf2-containing TFIIIB complex, forming a pre-initiation complex (PIC). Uniquely, SNAPc also recruits Pol II at the remaining splicesosomal snRNA genes (U1, 2, 4 and 5).
View Article and Find Full Text PDFMechanisms of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence.
bioRxiv
December 2024
Department of Biochemistry, Brandeis University, Waltham, MA 02453.
Transcription activators trigger transcript production by RNA Polymerase II (RNApII) via the Mediator coactivator complex. Here the dynamics of activator, Mediator, and RNApII binding at promoter DNA were analyzed using multi-wavelength single-molecule microscopy of fluorescently labeled proteins in budding yeast nuclear extract. Binding of Mediator and RNApII to the template required activator and an upstream activator sequence (UAS), but not a core promoter.
View Article and Find Full Text PDFTrypanosoma cruzi eIF4E3- and eIF4E4-containing complexes bind different mRNAs and may sequester inactive mRNAs during nutritional stress.
Nucleic Acids Res
December 2024
Carlos Chagas Institute, Oswaldo Cruz Foundation, FIOCRUZ, R. Prof. Algacyr Munhoz Mader 3775, 81350-010, Curitiba-PR, Brazil.
Many eIF4F and poly(A)-binding protein (PABP) paralogues are found in trypanosomes: six eIF4E, five eIF4G, one eIF4A and two PABPs. They are expressed simultaneously and assemble into different complexes, contrasting the situation in metazoans that use distinct complexes in different cell types/developmental stages. Each eIF4F complex has its own proteins, messenger RNAs (mRNAs) and, consequently, a distinct function.
View Article and Find Full Text PDFStructural characterization of the full-length Hantaan virus polymerase.
PLoS Pathog
December 2024
Division of Structural Biology, Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Article Synopsis
- Hantaviridae is a family of RNA viruses that includes pathogens affecting humans and animals, and they contain a polymerase essential for their genome replication.
- The study focuses on the expression and purification of the polymerase from the Hantaan virus, utilizing Cryo-EM to explore its structure in detail, achieving resolutions between 2.7 to 3.3 Å.
- Important findings include the identification of new conformations of the polymerase and the observation of its interaction with RNA and nucleotides, which provide insights into its transcription and replication mechanism, paving the way for potential therapeutic developments.
A function of TPL/TBL1-type corepressors is to nucleate the assembly of the preinitiation complex.
J Cell Biol
February 2025
Department of Biology, University of Washington, Seattle, WA, USA.
The plant corepressor TPL is recruited to diverse chromatin contexts, yet its mechanism of repression remains unclear. Previously, we leveraged the fact that TPL retains its function in a synthetic transcriptional circuit in the yeast model Saccharomyces cerevisiae to localize repressive function to two distinct domains. Here, we employed two unbiased whole-genome approaches to map the physical and genetic interactions of TPL at a repressed locus.
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