A5050559495- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Blood disorders and treatments
- Immunodeficiency and Autoimmune Disorders
- Peptidase Inhibition and Analysis
- Pneumocystis jirovecii pneumonia detection and treatment
- Genomics and Phylogenetic Studies
University of Fribourg
2020-2025
Universidad Nacional Autónoma de México
2017-2021
<h3>Background</h3> For the final step of maturation ribosome, nascent 40S and 60S subunits are exported from nucleus to cell cytoplasm. To prevent premature association these ribosomal subunits, eukaryotic initiation factor 6 (eIF6) binds subunit within nucleus. Its release in cytoplasm requires interaction EFL1 SDBS proteins. In Shwachman-Diamond syndrome (SDS), a defective protein prevents eIF6 eviction, inhibiting its recycle subsequent formation active 80S ribosome. <h3>Objective</h3>...
The biogenesis of eukaryotic ribosomes involves the ordered assembly around 80 ribosomal proteins. Supplying equimolar amounts assembly-competent proteins is complicated by their aggregation propensity and spatial separation location synthesis pre-ribosome incorporation. Recent evidence has highlighted that dedicated chaperones protect individual, unassembled on path to pre-ribosomal site. Here, we show co-translational recognition Rpl3 Rpl4 respective chaperone, Rrb1 or Acl4, reduces...
The early steps of large-ribosomal-subunit assembly feature among the least understood ribosome synthesis in eukaryotes. In Saccharomyces cerevisiae, box C/D chaperone small nucleolar ribonucleoprotein (snoRNP) snR190 and Npa1 complex, composed α-solenoid scaffold proteins Npa2, DEAD-box helicase Dbp6, RNA-binding protein Nop8, Rsa3, are likely involved 25S ribosomal RNA (rRNA) folding events. Here, we report for first time existence outside pre-ribosomal particles an independent...
Abstract Intrinsically disordered regions (IDRs) are highly enriched in the nucleolar proteome but their physiological role ribosome assembly remains poorly understood. Our study reveals functional plasticity of extremely abundant lysine-rich IDRs small ribonucleoprotein particles (snoRNPs) from protists to mammalian cells. We show Saccharomyces cerevisiae that electrostatic properties this IDR, KKE/D domain, promote snoRNP accumulation vicinity nascent rRNAs, facilitating modification....
Proteostasis needs to be tightly controlled meet the cellular demand for correctly de novo folded proteins and avoid protein aggregation. While a coupling between translation rate co-translational folding, likely involving an interplay ribosome its associated chaperones, clearly appears exist, underlying mechanisms contribution of ribosomal remain explored. The uL3 contains long internal loop whose tip region is in close proximity peptidyl transferase center. Intriguingly, rpl3[W255C]...
The Shwachman-Diamond Syndrome (SDS) is a disorder arising from mutations in the genes encoding for Shwachman-Bodian-Diamond (SBDS) protein and GTPase known as Elongation Factor Like-1 (EFL1). Together, these proteins remove anti-association factor eIF6 surface of pre-60S ribosomal subunit to promote formation mature ribosomes. SBDS missense can either destabilize fold or affect epitopes. molecular alterations resulting latter remain largely unknown, although some evidence suggest that...
The dynamism of proteins is central to their function, and several have been described as flexible, consisting multiple domains joined by flexible linkers, even intrinsically disordered. Several techniques exist study protein structures, but small angle X-ray scattering (SAXS) has proven be particularly powerful for the quantitative analysis such systems. In present report, we used SAXS in combination with crystallography highlight usefulness at characterizing proteins, using examples two...
Abstract The early steps of large-ribosomal-subunit assembly feature among the least understood ribosome synthesis in eukaryotes. In Saccharomyces cerevisiae , snR190 box C/D snoRNP chaperone and Npa1 complex, composed α-solenoid scaffold proteins Npa2, DEAD-box helicase Dbp6, RNA-binding protein Nop8 Rsa3, are likely involved 25S rRNA folding events. Here, we report for first time existence outside pre-ribosomal particles an independent macromolecular constituted by complex chaperone....
Ribosome biogenesis is closely linked to the cell growth and proliferation.Dysregulation of this process causes several diseases collectively known as ribosomopathies.For final step maturation ribosome, nascent 40S 60S subunits are exported from nucleus cytoplasm.To prevent premature association these ribosomal subunits, eukaryotic initiation factor 6 (eIF6) binds subunit within nucleus.Its release in cytoplasm requires interaction EFL1 SDBS proteins.In Shwachman-Diamond syndrome (SDS), a...
Abstract The biogenesis of eukaryotic ribosomes involves the ordered assembly around 80 ribosomal proteins. Supplying equimolar amounts assembly-competent proteins is complicated by their aggregation propensity and spatial separation location synthesis pre-ribosome incorporation. Recent evidence has highlighted that dedicated chaperones protect individual, unassembled on path to pre-ribosomal site. Here, we show co-translational recognition Rpl3 Rpl4 respective chaperone, Rrb1 or Acl4,...