P-stalk ribosomes act as master regulators of cytokine-mediated processes.

Inflammatory cytokines are pivotal to immune responses. Upon cytokine exposure, cells enter an "alert state" that enhances their visibility to the immune system. Here, we identified an alert-state subpopulation of ribosomes defined by the presence of the P-stalk.

Ribosome specialization in cancer: a spotlight on ribosomal proteins.

In the past few decades, our view of ribosomes has changed substantially. Rather than passive machines without significant variability, it is now acknowledged that they are heterogeneous, and have direct regulatory capacity. This 'ribosome heterogeneity' comes in many flavors, including in both the RNA and protein components of ribosomes, so there are many paths through which ribosome specialization could arise.

Visualization of translation reorganization upon persistent ribosome collision stress in mammalian cells.

Aberrantly slow ribosomes incur collisions, a sentinel of stress that triggers quality control, signaling, and translation attenuation. Although each collision response has been studied in isolation, the net consequences of their collective actions in reshaping translation in cells is poorly understood. Here, we apply cryoelectron tomography to visualize the translation machinery in mammalian cells during persistent collision stress.

Proteome diversification by mRNA translation in cancer.

mRNA translation is a highly conserved and tightly controlled mechanism for protein synthesis and is well known to be altered by oncogenes to promote cancer development. This distorted mRNA translation is accompanied by the vulnerability of cancer to inhibitors of key mRNA translation components. Novel studies also suggest that these alternations could be utilized for immunotherapy.

Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential.

The use of alternative promoters, splicing, and cleavage and polyadenylation (APA) generates mRNA isoforms that expand the diversity and complexity of the transcriptome. Here, we uncovered thousands of previously undescribed 5' uncapped and polyadenylated transcripts (5' UPTs). We show that these transcripts resist exonucleases due to a highly structured RNA and N6-methyladenosine modification at their 5' termini.

Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation.

The small intestine is a rapidly proliferating organ that is maintained by a small population of Lgr5-expressing intestinal stem cells (ISCs). However, several Lgr5-negative ISC populations have been identified, and this remarkable plasticity allows the intestine to rapidly respond to both the local environment and to damage. However, the mediators of such plasticity are still largely unknown.

mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K.

Increased protein synthesis supports the rapid cell proliferation associated with cancer. The mutant mouse reduces the expression of the ribosomal protein RPL24 and has been used to suppress translation and limit tumorigenesis in multiple mouse models of cancer. Here, we show that also suppresses tumorigenesis and proliferation in a model of colorectal cancer (CRC) with two common patient mutations, and .

Translation initiation and its relevance in colorectal cancer.

Protein synthesis is one of the most essential processes in every kingdom of life, and its dysregulation is a known driving force in cancer development. Multiple signaling pathways converge on the translation initiation machinery, and this plays a crucial role in regulating differential gene expression. In colorectal cancer, dysregulation of initiation results in translational reprogramming, which promotes the selective translation of mRNAs required for many oncogenic processes.