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.

eIF4F complex dynamics are important for the activation of the integrated stress response.

In response to stress, eukaryotes activate the integrated stress response (ISR) via phosphorylation of eIF2α to promote the translation of pro-survival effector genes, such as GCN4 in yeast. Complementing the ISR is the target of rapamycin (TOR) pathway, which regulates eIF4E function. Here, we probe translational control in the absence of eIF4E in Saccharomyces cerevisiae.

The tRNA methyltransferase TrmB is critical for stress responses and pulmonary infection.

As deficiencies in tRNA modifications have been linked to human diseases such as cancer and diabetes, much research has focused on the modifications' impacts on translational regulation in eukaryotes. However, the significance of tRNA modifications in bacterial physiology remains largely unexplored. In this paper, we demonstrate that the mG tRNA methyltransferase TrmB is crucial for a top-priority pathogen, , to respond to stressors encountered during infection, including oxidative stress, low pH, and iron deprivation.

Translating while under attack: Plant defense mRNAs find a way.

In plants, pattern-triggered immunity shuts down global translation while allowing the translation of defense mRNAs. Wang et al. (2022) describe a previously unknown mechanism for how elements in the 5' UTR of these mRNAs can recruit the translation machinery to initiate protein synthesis.

N1-methylpseudouridine found within COVID-19 mRNA vaccines produces faithful protein products.

Synthetic mRNA technology is a promising avenue for treating and preventing disease. Key to the technology is the incorporation of modified nucleotides such as N1-methylpseudouridine (m1Ψ) to decrease immunogenicity of the RNA. However, relatively few studies have addressed the effects of modified nucleotides on the decoding process.

Canary in a coal mine: collided ribosomes as sensors of cellular conditions.

The recent discovery that collision of ribosomes triggers quality control and stress responses in eukaryotes has shifted the perspective of the field. Collided eukaryotic ribosomes adopt a unique structure, acting as a ubiquitin signaling platform for various response factors. While several of the signals that determine which downstream pathways are activated have been uncovered, we are only beginning to learn how the specificity for the activation of each process is achieved during collisions.

Alkylative damage of mRNA leads to ribosome stalling and rescue by translation in bacteria.

Similar to DNA replication, translation of the genetic code by the ribosome is hypothesized to be exceptionally sensitive to small chemical changes to its template mRNA. Here we show that the addition of common alkylating agents to growing cultures of leads to the accumulation of several adducts within RNA, including N(1)-methyladenosine (mA). As expected, the introduction of mA to model mRNAs was found to reduce the rate of peptide bond formation by three orders of magnitude in a well-defined in vitro system.

The snoRNA target of t(4;14) in multiple myeloma regulates ribosome biogenesis.

The orphan small nucleolar RNA (snoRNA) ACA11 is overexpressed as a result of the t(4;14) chromosomal translocation in multiple myeloma (MM), increases reactive oxygen species, and drives cell proliferation. Like other snoRNAs, ACA11 is predominantly localized to a sub-nuclear organelle, the nucleolus. We hypothesized that increased ACA11 expression would increase ribosome biogenesis and protein synthesis.

Interactions between the mRNA and Rps3/uS3 at the entry tunnel of the ribosomal small subunit are important for no-go decay.

No-go Decay (NGD) is a process that has evolved to deal with stalled ribosomes resulting from structural blocks or aberrant mRNAs. The process is distinguished by an endonucleolytic cleavage prior to degradation of the transcript. While many of the details of the pathway have been described, the identity of the endonuclease remains unknown.