Insight on Research


New insights into how peptides became a part of the ancient RNA world

Peptides from the ribosome of T. thermophilus

In all present-day organisms, information encoded in DNA, the genetic material of the cell, is converted via an RNA intermediate into proteins, the molecular machines of the cell. However, evidence suggests that in a distant evolutionary past our single-celled ancestors used only RNA for both genetic information storage and metabolism. A cornerstone of this “RNA world” would have been an RNA able to replicate itself.

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The idiosyncratic ribosomes of mitochondria

The overall structure of the complete yeast mitoribosome

Mitochondria are organelles within eukaryotic cells that likely evolved from an ancient bacterium that was engulfed by a primordial eukaryote. Within mitochondria, mitochondrial ribosomes (mitoribosomes) synthesise a subset of essential proteins encoded by the mitochondrial genome.

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Uncovering the molecular basis of triage during protein synthesis

Diagram of triage during protein synthesis

Every minute, cells make millions of new proteins which must be transported to the correct location, folded, modified and assembled with other proteins in order to function properly. Failure at any of these maturation steps can reduce protein function and lead to the accumulation of aberrant protein intermediates, resulting in disease.

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IL-17, a regulator of the immune system, impacts behaviour

Mutant worms feeding alone

The state of the immune system has effects on brain function, but despite suggestions that immunoregulators can affect people’s mood and behaviour, we are only beginning to understand how these two major body systems interact. The contributions of a neuron to circuit activity and behaviour depend on its responsiveness to upstream inputs, and its ability to drive downstream outputs.

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New insights into the structure and dynamics of the catalytic spliceosome

Cartoon representation of the structure of a yeast spliceosome captured just before mRNA formation. Note how second step factors bind on the side of the complex and stabilize the position of the branch helix, thus making space for the 3’-end of the intron in the active site.

The spliceosome is a molecular machine, which together with RNA polymerases and ribosomes plays a critical role in basic gene expression. Research by Kiyoshi Nagai’s group in the LMB’s Structural Studies Division, has previously revealed the structure of the spliceosome in a fully active, substrate-bound state, immediately after its first catalytic reaction. The group has now expanded upon this work revealing the near-atomic level structure of the spliceosome just before mRNA formation.

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New hypothesis for the formation of macropinocytic cups

Dictyostelium cell making four macropinosomes, each of which is organised around a patch of PIP3 (orange) with SCAR/WAVE recruited to its perimeter (green)

Macropinocytosis, the cellular uptake of fluids from the environment, is employed by a variety of cells and requires the formation of a cup-shaped structure that protrudes from the cell’s surface and captures gulps of medium. Polymerisation of actin under the plasma membrane drives the extension of macropinocytic cups. However, until now it has been unclear how the actin forming the walls of the cup is shaped into a ring.

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Recovering stalled ribosomes

ArfA and RF2 bound to the bacterial ribosome

Ribosomes are cellular molecular machines that link amino acids together in the order specified by messenger RNA (mRNA) to make proteins. Near the end of the mRNA molecule a specific nucleotide sequence, known as a stop codon, signals for protein synthesis to terminate by recruiting release factors that release the newly made protein from the ribosome and recycle the ribosome to start another round of protein synthesis.
However, some mRNA molecules are defective.

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New technologies enable systematic recoding of genomes

GENESIS via REXER schematic

The design and synthesis of genomes provides a powerful approach for understanding and engineering biology. The development of methods that can accurately replace the genome in sections, provide feedback on precisely where a given design fails and on how to repair it, and that can be rapidly repeated for whole genome replacement would accelerate our ability to understand and manipulate the information encoded in genomes. Using E.

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New insights into the mechanism of ubiquitin chain cleavage

Cezanne–Lys11 diubiquitin complex structure

The ubiquitin system is a complex system in all eukaryotic organisms involved in the regulation of most cellular processes. A huge variety of signals are assembled with ubiquitin molecules onto cellular proteins to mark them for a specific task. Important regulators of the ubiquitin system are deubiquitinating enzymes (DUBs), which remove, or cleave, ubiquitin chains in order to reverse these modifications.

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Molecular mechanism triggering assembly of the Wnt signalosome uncovered

Model of Wnt signalosome assembly by domain swapping of Dishevelled (DVL)

The Wnt signaling pathway is an ancient cell communication pathway that has important roles in development and cancer. For the first time, work by Mariann Bienz’s group in the LMB’s PNAC Division has uncovered the molecular mechanism triggering the assembly of the Wnt signalosome, a key component of the Wnt signal transduction pathway that controls normal development and tissue homeostasis in all animals.

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