Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes.

In yeast, multiprotein bridging factor 1 (Mbf1) has been proposed to function in the integrated stress response (ISR) as a transcriptional coactivator by mediating a direct interaction between general transcription machinery and the process's key effector, Gcn4. However, mounting evidence has demonstrated that Mbf1 (and its human homolog EDF1) is recruited to collided ribosomes, a known activator of the ISR. In this study, we connect these otherwise seemingly disparate functions of Mbf1.

The RNA helicase HrpA rescues collided ribosomes in .

Although many antibiotics inhibit bacterial ribosomes, loss of known factors that rescue stalled ribosomes does not lead to robust antibiotic sensitivity in , suggesting the existence of additional mechanisms. Here, we show that the RNA helicase HrpA rescues stalled ribosomes in Acting selectively on ribosomes that have collided, HrpA uses ATP hydrolysis to split stalled ribosomes into subunits. Cryo-EM structures reveal how HrpA simultaneously binds to two collided ribosomes, explaining its selectivity, and how its helicase module engages downstream mRNA, such that by exerting a pulling force on the mRNA, it would destabilize the stalled ribosome.

Theoretical infrared spectroscopy of protonated methane isotopologues.

The vibrational spectroscopy of protonated methane and its mixed hydrogen/deuterium isotopologues remains a challenge to both experimental and computational spectroscopy due to the iconic floppiness of CH. Here, we compute the finite-temperature broadband infrared spectra of CH and all its isotopologues, CHD up to CD, from path integral molecular dynamics in conjunction with interactions and dipoles computed consistently at CCSD(T) coupled cluster accuracy. The potential energy and dipole moment surfaces have been accurately represented in full dimensionality in terms of high-dimensional neural networks.

Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline.

Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear.

SnapShot: Eukaryotic ribosome biogenesis II.

Ribosome production is essential for cell growth. Approximately 200 assembly factors drive this complicated pathway that starts in the nucleolus and ends in the cytoplasm. A large number of structural snapshots of the pre-60S pathway have revealed the principles behind large subunit synthesis.