Synthesis of ribosomal RNA by RNA polymerase I (RNA pol I) is an elemental biological process and is key for cellular homeostasis. In a forward genetic screen in C. elegans designed to identify DNA damage-response factors, we isolated a point mutation of RNA pol I, rpoa-2(op259), that leads to altered rRNA synthesis and a concomitant resistance to ionizing radiation (IR)-induced germ cell apopt...

Trans-translation is a ubiquitous bacterial mechanism for ribosome rescue in the event of translation stalling. Although trans-translation is not essential in several bacterial species, it has been found essential for viability or virulence in a wide range of pathogens. We describe here that trans-translation is essential in the human pathogen Legionella pneumophila, the etiologic agent of Legi...

Although co-translational biological processes attract much attention, no general and easy method has been available to detect cellular nascent polypeptide chains, which we propose to call collectively a "nascentome." We developed a method to selectively detect polypeptide portions of cellular polypeptidyl-tRNAs and used it to study the generality of the quality control reactions that rescue de...

In Saccharomyces cerevisiae, ribosomal protein gene (RPG) promoters display binding sites for either Rap1 or Abf1 transcription factors. Unlike Rap1-associated promoters, the small cohort of Abf1-dependent RPGs (Abf1-RPGs) has not been extensively investigated. We show that RPL3, RPL4B, RPP1A, RPS22B and RPS28A/B share a common promoter architecture, with an Abf1 site upstream of a conserved el...

In the current issue, Richter et al (2010) show that mammalian mitochondrial ribosomes contain a ribosomal protein (ICT1) that acts as a ribosome-dependent, codonindependent peptidyl-tRNA hydrolase. This ribosomal protein can rescue ribosomes stalled on mRNAs lacking a termination codon. Every translational system runs into trouble when it encounters mRNAs that have lost the translation termina...

The surveillance of mRNA translation is imperative for homeostasis. Monitoring the integrity of the message is essential, as the translation of aberrant mRNAs leads to stalling of the translational machinery. During ribosomal rescue, arrested ribosomes are specifically recognized by the conserved eukaryotic proteins Dom34 and Hbs1, to initiate their recycling. Here we solve the structure of Dom...

In the translation process, translating ribosomes usually move on an mRNA until they reach the stop codon. However, when ribosomes translate an aberrant mRNA, they stall. Then, ribosomes are rescued from the aberrant mRNA, and the aberrant mRNA is subsequently degraded. In eukaryotes, Pelota (Dom34 in yeast) and Hbs1 are responsible for solving general problems of ribosomal stall in translation...

Transcription Factor 4 (TCF4) is a clinically pleiotropic gene associated with schizophrenia and Pitt-Hopkins syndrome (PTHS). To gain insight about the neurobiology of TCF4, we created an in vivo model of PTHS by suppressing Tcf4 expression in rat prefrontal neurons immediately prior to neurogenesis. This cell-autonomous genetic insult attenuated neuronal spiking by increasing the afterhyperpo...