Several pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is unclear. Here, we show that reduced levels of the conserved RNA methyltransferase NSUN5 increase the lifespan and stress resistance in yeast, worms and flies. Rcm1, the yeast homologue of NSUN5, methylates C2278 within a conserved region of 25S rRNA. Loss of Rcm1 alters the structural conformation of the ribosome in close proximity to C2278, as well as translational fidelity, and favours recruitment of a distinct subset of oxidative stress-responsive mRNAs into polysomes. Thus, rather than merely being a static molecular machine executing translation, the ribosome exhibits functional diversity by modification of just a single rRNA nucleotide, resulting in an alteration of organismal physiological behaviour, and linking rRNA-mediated translational regulation to modulation of lifespan, and differential stress response.

In Hypocrea jecorina, Xyr1 (xylanase regulator 1) is the main transcription activator of hydrolase-encoding genes, such as xyn1, xyn2, bxl1, cbh1, cbh2, egl1, and bgl1. Even though Xyr1 mediates the induction signal for all these genes derived from various inducing carbon sources and compounds, xyr1 transcription itself is not inducible by any of these substances. However, cultivation on glucose as the carbon source provokes carbon catabolite repression of xyr1 transcription mediated by Cre1. In addition, xyr1 transcription is repressed by the specific transcription factor Ace1. Moreover, Xyr1 is permanently available in the cell, and no de novo synthesis of this factor is needed for a first induction of xyn1 transcription. The constitutive expression of xyr1 leads to a significant elevation/deregulation of the xyn1, xyn2, and bxl1 transcription compared to what is seen for the parental strain. Overall, the corresponding xylanolytic enzyme activities are clearly elevated in a constitutively xyr1-expressing strain, emphasizing this factor as an auspicious target for genetically engineered strain improvement.

The methylotrophic yeast Pichia pastoris is widely used in the manufacture of industrial enzymes and pharmaceuticals. Like most biotechnological production hosts, P. pastoris is heterotrophic and grows on organic feedstocks that have competing uses in the production of food and animal feed. In a step toward more sustainable industrial processes, we describe the conversion of P. pastoris into an autotroph that grows on CO 2 . By addition of eight heterologous genes and deletion of three Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: