Pre-print out now: UFMylation orchestrates early rDNA repair events
Great work spearheaded by Sonny Panichnantakul in the lab: https://doi.org/10.1101/2024.02.14.580383
Great work in Mol Cell by Pierre Bensidoun in a joint effort by the Oeffinger and Zenklusen labs: an mRNA-dependent mechanism for the functionalization and heterogeneity of NPCs in budding yeast through nuclear basket assembly.
Happy to announce that the Oeffinger Lab has been awarded an NSERC Discovery grant to study the spatial arrangement, stoichiometry, and substrate specificity of nuclear mRBPs in S.cerevisiae.
Happy to announce that the Oeffinger Lab has been awarded a CHIR Project grant together with the Zenklusen Lab to work on TPR and RNA homeostasis!
Announcing the publication of “The Biology of mRNA: Structure and Function” (Springer Nature) with my co-editor Daniel Zenklusen.
Post-doc position available
The lab is looking for a highly-motivated post-doctoral fellow trained in biochemistry for a recently funded shared project with Dr. Jackie Vogel’s Lab (McGill University) investigating the role of phosphorylation of gamma-tubulin in spindle stability and function using Mass spectrometry. Applicants should have a solid background in biochemical approaches including recombinant protein purifications, FPLC/HPLC, and kinase assays, or similar.
Prospective graduate students with knowledge and interest in biochemical approaches and a competitive GPA are also encouraged to apply.
Cellular senescence is a tumor suppressor programme characterized by a stable cell cycle arrest. Here we report that cellular senescence triggered by a variety of stimuli leads to diminished ribosome biogenesis and the accumulation of both rRNA pre-cursors and ribosomal proteins. These defects were associated with reduced expression of several ribosome biogenesis factors, the knockdown of which was also sufficient to induce senescence. Genetic analysis revealed that Rb but not p53 was required for the senescence response to altered ribosome biogenesis. Mechanistically, the ribosomal protein S14 (RPS14 or uS11) accumulates in the soluble non-ribosomal fraction of senescent cells, where it binds and inhibits CDK4 (cyclin-dependent kinase 4). Overexpression of RPS14 is sufficient to inhibit Rb phosphorylation, inducing cell cycle arrest and senescence. Here we describe a mechanism for maintaining the senescent cell cycle arrest that may be relevant for cancer therapy, as well as biomarkers to identify senescent cells.
Daniel Scott has won the 2018 Richard Rabasa-Lhoret Prize for his talk on Paraspeckles and ALS at the IRCM Scientific Forum. Congratulations, Dan!
Nol12 is a multifunctional RNA binding protein at the nexus of RNA and DNA metabolism
Nol12 is a multifunctional RBP with roles in RNA metabolism and genome maintenance, Read More
While the protein composition of various yeast 60S ribosomal subunit assembly intermediates has been studied in detail, little is known about ribosomal RNA (rRNA) structural rearrangements that take place during early 60S assembly steps. Using a high- throughput RNA structure probing method, we provide nucleotide resolution insights into rRNA structural rearrangements during nucleolar 60S assembly. Our results suggest that many rRNA-folding steps, such as folding of 5.8S rRNA, occur at a very specific stage of assembly, and propose that downstream nuclear assembly events can only continue once 5.8S folding has been completed. Our maps of nucleotide flexibility enable making predictions about the establishment of protein–rRNA interactions, providing intriguing insights into the temporal order of protein–rRNA as well as long-range inter-domain rRNA interactions. These data argue that many distant domains in the rRNA can assemble simultaneously during early 60S assembly and underscore the enormous complexity of 60S synthesis.
Non-coding RNAs have critical roles in biological processes, and RNA chaperones can promote their folding into the native shape required for their function. La proteins are a class of highly abundant RNA chaperones that contact pre-tRNAs and other RNA polymerase III transcripts via their common UUU-3′OH ends, as well as through less specific contacts associated with RNA chaperone activity. However, whether La proteins preferentially bind misfolded pre-tRNAs or instead engage all pre-tRNA substrates irrespective of their folding status is not known. La deletion in yeast is synthetically lethal when combined with the loss of tRNA modifications predicted to contribute to the native pre-tRNA fold, such as the N2, N2-dimethylation of G26 by the methyltransferase Trm1p. In this work, we identify G26 containing pre-tRNAs that misfold in the absence of Trm1p and/or La (Sla1p) in Schizosaccharomyces pombe cells, then test whether La preferentially associates with such tRNAs in vitro and in vivo. Our data suggest that La does not discriminate a native from misfolded RNA target, and highlights the potential challenges faced by RNA chaperones in preferentially binding defective substrates.
Carolina wins prize at 50th-year celebration of Université de Montréal
Oeffinger Lab 