scholarly journals Inhibiting eukaryotic ribosome biogenesis: Mining new tools for basic research and medical applications

2019 ◽  
Vol 6 (10) ◽  
pp. 491-493
Author(s):  
Lisa Kofler ◽  
Michael Prattes ◽  
Helmut Bergler
Keyword(s):  
Ribosome Biogenesis ◽  
Basic Research ◽  
Medical Applications ◽  
Eukaryotic Ribosome

Spin polarized 3He: From basic research to medical applications

2013 ◽  
Vol 44 (6) ◽  
pp. 904-908 ◽  
Author(s):  
S. Karpuk ◽  
F. Allmendinger ◽  
M. Burghoff ◽  
C. Gemmel ◽  
M. Güldner ◽  
...  
Keyword(s):  
Basic Research ◽  
Medical Applications ◽  
Spin Polarized

De novo design of α-helical proteins: basic research to medical applications

1996 ◽  
Vol 74 (2) ◽  
pp. 133-154 ◽  
Author(s):  
Robert S. Hodges
Keyword(s):  
Protein Folding ◽  
De Novo ◽  
Coiled Coil ◽  
Basic Research ◽  
De Novo Design ◽  
Coiled Coils ◽  
Medical Applications ◽  
Dimerization Domain ◽  
Recombinant Peptides ◽  
Helical Proteins

The two-stranded α-helical coiled-coil is a universal dimerization domain used by nature in a diverse group of proteins. The simplicity of the coiled-coil structure makes it an ideal model system to use in understanding the fundamentals of protein folding and stability and in testing the principles of de novo design. The issues that must be addressed in the de novo design of coiled-coils for use in research and medical applications are (i) controlling parallel versus antiparallel orientation of the polypeptide chains, (ii) controlling the number of helical strands in the assembly (iii) maximizing stability of homodimers or heterodimers in the shortest possible chain length that may require the engineering of covalent constraints, and (iv) the ability to have selective heterodimerization without homodimerization, which requires a balancing of selectivity versus affinity of the dimerization strands. Examples of our initial inroads in using this de novo design motif in various applications include: heterodimer technology for the detection and purification of recombinant peptides and proteins; a universal dimerization domain for biosensors; a two-stage targeting and delivery system; and coiled-coils as templates for combinatorial helical libraries for basic research and drug discovery and as synthetic carrier molecules. The universality of this dimerization motif in nature suggests an endless number of possibilities for its use in de novo design, limited only by the creativity of peptide–protein engineers.Key words: de novo design of proteins, α-helical coiled-coils, protein folding, protein stability, dimerization domain, dimerization motif.

scholarly journals A network of assembly factors is involved in remodeling rRNA elements during preribosome maturation

2014 ◽  
Vol 207 (4) ◽  
pp. 481-498 ◽  
Author(s):  
Jochen Baßler ◽  
Helge Paternoga ◽  
Iris Holdermann ◽  
Matthias Thoms ◽  
Sander Granneman ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Ribosome Biogenesis ◽  
Ribosome Assembly ◽  
Functional Importance ◽  
Peptidyl Transferase ◽  
Peptidyl Transferase Center ◽  
Eukaryotic Ribosome ◽  
Assembly Factors

Eukaryotic ribosome biogenesis involves ∼200 assembly factors, but how these contribute to ribosome maturation is poorly understood. Here, we identify a network of factors on the nascent 60S subunit that actively remodels preribosome structure. At its hub is Rsa4, a direct substrate of the force-generating ATPase Rea1. We show that Rsa4 is connected to the central protuberance by binding to Rpl5 and to ribosomal RNA (rRNA) helix 89 of the nascent peptidyl transferase center (PTC) through Nsa2. Importantly, Nsa2 binds to helix 89 before relocation of helix 89 to the PTC. Structure-based mutations of these factors reveal the functional importance of their interactions for ribosome assembly. Thus, Rsa4 is held tightly in the preribosome and can serve as a “distribution box,” transmitting remodeling energy from Rea1 into the developing ribosome. We suggest that a relay-like factor network coupled to a mechano-enzyme is strategically positioned to relocate rRNA elements during ribosome maturation.

scholarly journals Potent, Reversible, and Specific Chemical Inhibitors of Eukaryotic Ribosome Biogenesis

Cell ◽  
2016 ◽  
Vol 167 (2) ◽  
pp. 512-524.e14 ◽  
Author(s):  
Shigehiro A. Kawashima ◽  
Zhen Chen ◽  
Yuki Aoi ◽  
Anupam Patgiri ◽  
Yuki Kobayashi ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Specific Chemical ◽  
Eukaryotic Ribosome ◽  
Chemical Inhibitors

scholarly journals Inhibiting eukaryotic ribosome biogenesis

BMC Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Dominik Awad ◽  
Michael Prattes ◽  
Lisa Kofler ◽  
Ingrid Rössler ◽  
Mathias Loibl ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Eukaryotic Ribosome

scholarly journals Tuning the ribosome: The influence of rRNA modification on eukaryotic ribosome biogenesis and function

RNA Biology ◽  
2016 ◽  
Vol 14 (9) ◽  
pp. 1138-1152 ◽  
Author(s):  
Katherine E. Sloan ◽  
Ahmed S. Warda ◽  
Sunny Sharma ◽  
Karl-Dieter Entian ◽  
Denis L. J. Lafontaine ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Eukaryotic Ribosome ◽  
And Function

scholarly journals Arabidopsis REI-LIKE proteins activate ribosome biogenesis during cold acclimation

2020 ◽  
Author(s):  
Bo Eng Cheong ◽  
Olga Beine-Golovchuk ◽  
Michal Gorka ◽  
William Wing Ho Ho ◽  
Federico Martinez-Seidel ◽  
...  
Keyword(s):  
Steady State ◽  
Feedback Control ◽  
Cold Acclimation ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Transcriptional Control ◽  
De Novo ◽  
Eukaryotic Ribosome ◽  
Steady State Temperature

AbstractArabidopsis REIL proteins are cytosolic ribosomal 60S-biogenesis factors. After shift to 10°C, reil mutants deplete and slowly replenish non-translating eukaryotic ribosome complexes of root tissue, while tightly controlling the balance of non-translating 40S- and 60S-subunits. Reil mutations compensate by hyper-accumulation of non-translating subunits at steady-state temperature; after cold-shift, a KCl-sensitive 80S sub-fraction remains depleted. We infer that Arabidopsis buffers fluctuating translation by pre-existing non-translating ribosomes before de novo synthesis meets temperature-induced demands. Reil1 reil2 double mutants accumulate 43S-preinitiation and pre-60S-maturation complexes and have altered paralog composition of ribosomal proteins in non-translating complexes. With few exceptions, e.g. RPL3B and RPL24C, these changes are not under transcriptional control. Our study suggests requirement of de novo synthesis of eukaryotic ribosomes for long-term cold acclimation, feedback control of NUC2 and eIF3C2 transcription and links new proteins, AT1G03250, AT5G60530, to plant ribosome biogenesis. We propose that Arabidopsis requires biosynthesis of specialized ribosomes for cold acclimation.Highlight of this studyREIL proteins affect paralog composition of eukaryotic ribosomes and suppress accumulation of 43S-preinitiation and pre-60S-maturation complexes, suggesting functions of ribosome heterogeneity and biogenesis in plant cold acclimation.

scholarly journals Eukaryotic ribosome biogenesis at a glance

2013 ◽  
Vol 126 (21) ◽  
pp. 4815-4821 ◽  
Author(s):  
E. Thomson ◽  
S. Ferreira-Cerca ◽  
E. Hurt
Keyword(s):  
Ribosome Biogenesis ◽  
Eukaryotic Ribosome

scholarly journals Shaping the Nascent Ribosome: AAA-ATPases in Eukaryotic Ribosome Biogenesis

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 715 ◽  
Author(s):  
Prattes ◽  
Lo ◽  
Bergler ◽  
Stanley
Keyword(s):  
Molecular Mechanism ◽  
Ribosome Biogenesis ◽  
Current Knowledge ◽  
Target Recognition ◽  
Efficient Removal ◽  
Ribonucleoprotein Complex ◽  
Eukaryotic Ribosome ◽  
Macromolecular Assemblies ◽  
Chemical Complex ◽  
Aaa Atpases

AAA-ATPases are molecular engines evolutionarily optimized for the remodeling of proteins and macromolecular assemblies. Three AAA-ATPases are currently known to be involved in the remodeling of the eukaryotic ribosome, a megadalton range ribonucleoprotein complex responsible for the translation of mRNAs into proteins. The correct assembly of the ribosome is performed by a plethora of additional and transiently acting pre-ribosome maturation factors that act in a timely and spatially orchestrated manner. Minimal disorder of the assembly cascade prohibits the formation of functional ribosomes and results in defects in proliferation and growth. Rix7, Rea1, and Drg1, which are well conserved across eukaryotes, are involved in different maturation steps of pre-60S ribosomal particles. These AAA-ATPases provide energy for the efficient removal of specific assembly factors from pre-60S particles after they have fulfilled their function in the maturation cascade. Recent structural and functional insights have provided the first glimpse into the molecular mechanism of target recognition and remodeling by Rix7, Rea1, and Drg1. Here we summarize current knowledge on the AAA-ATPases involved in eukaryotic ribosome biogenesis. We highlight the latest insights into their mechanism of mechano-chemical complex remodeling driven by advanced cryo-EM structures and the use of highly specific AAA inhibitors.

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