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William Hagen, Violin and Orion Weiss, Piano
No full text2019, March 29
William Hagen, violin; Orion Weiss, piano, performed Mozart: Violin Sonata in A Major, K. 526; Brahms: Violin Sonata No. 3 in D Minor, Op. 8; Schubert: Rondo in B Minor, D. 895.https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1035/thumbnail.jp
Mid-century glassware from Erway Glass Blowing
No full textMid-century glassware from Erway Glass Blowing, Oregon
Courtesy of Laboratory Safety Department
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/the-evolving-campus/1060/thumbnail.jp
A Stress-Induced TRNA Depletion Response Mediates Codon-Based Translational Repression and Growth Suppression
Get PDFEukaryotic transfer RNAs (tRNAs) can become fragmented upon various cellular stresses, generating tRNA-derived RNA fragments (tRFs). Though this process has been observed for numerous cellular stresses and in many species ranging from plant cells to yeast and human cells, it is still poorly characterized and understood. Such tRNA fragmentation has previously been thought to affect a small fraction of the tRNA pool and was thus presumed to not affect the role of tRNAs in translation. We report that in human cells, oxidative stress can rapidly generate tRFs derived from tyrosyl tRNAGUA—resulting in a significant depletion of the precursor tRNA molecule and mature tRNA while also leading to elevated levels of the tRF. Proteomic and ribosomal profiling of tyrosyl tRNAGUA-depleted cells revealed impaired expression of proteins enriched in its cognate tyrosine codons, comprising growth and metabolic genes. Consistent with these affected pathways, depletion of tyrosyl tRNAGUA or its downstream targets, EPCAM, SCD, or USP3, repressed growth—revealing a tRNA-dependent growth suppressive pathway for oxidative stress response. A synthetic mimetic of the tRF induced upon oxidative stress was used to identify interactions with RNA binding proteins through mass spectrometry. High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) of hnRNPA1 and SSB confirmed the mass spectrometry results and identified endogenous reciprocal interactions between the protein and tRF. Binding of this tRF to hnRNPA1 inhibits destabilization of endogenous targets of this RNA binding protein, leading to increased mRNA expression of DNA damage response and cell cycle regulatory genes. Thus, tRNA fragmentation can both deplete a precursor tRNA molecule with codon-dependent regulatory consequences and also generate small-RNAs that can interact with and regulate RNA binding proteins
Interview with Dr. Libchaber for the American Institute of Physics, Oral History Collection, by Eric D. Siggia
Get PDFElucidation of the Functional Architecture of the Early Pre-Ribosomal Processing Machinery in Yeast
Get PDFRibosomes carry out one of the most fundamental functions of life - the translation of genetic information into functional proteins. The pivotal role of the ribosome in the cell is reflected in its immensely complicated and energy-consuming assembly pathway. The maturation of a eukaryotic ribosome involves more than 200 non-ribosomal factors and the activity of all three RNA polymerases. In yeast, ribosome biogenesis starts with the transcription of the 35S pre-ribosomal RNA in the nucleolus. This large RNA molecule contains three of the four ribosomal RNAs separated by several internal and external transcribed spacer regions. The 5\u27 external transcribed spacer (5\u27ETS) is the first RNA domain of the 35S pre-rRNA being transcribed. As it emerges from the RNA polymerase it is bound by UtpA, a 660 kDa complex consisting of 7 essential subunits in yeast. 9 By binding to the nascent pre-rRNA, UtpA triggers the association of multiple other proteins and complexes, which leads to the formation of the ~2 MDa 5\u27 ETS particle. As transcription continues through the ensuing small subunit rRNA gene more ribosome biogenesis factors as well as ribosomal proteins are recruited and the 5\u27 ETS particle evolves into the small subunit processome. The small subunit processome, a giant particle, unique and essential to eukaryotes, coordinates the cleavage of the 35S pre-rRNA to separate the maturation of the small and large ribosomal subunit. So far, a functional understanding of the initial events in ribosome biogenesis has been impeded by a lack of structural and biochemical data about the protein complexes facilitating this process and the pre-ribosomal particles they form. To gain mechanistic insights into these earliest steps we set out to delineate the role of UtpA as first building block, vital structural component and organizer of the 5\u27 ETS particle and the small subunit processome. By using protein-protein and RNA-protein cross-linking techniques combined with negative stain electron microscopy and biochemical assays we were able to define the composite RNA binding site of UtpA and characterize its molecular architecture in the absence of high-resolution structural data (Chapter II). Subsequent structure determination of the small subunit processome by cryoelectron microscopy has not only provided the first fully assigned atomic model of UtpA but visualized how ribosome biogenesis factors keep the ribosomal RNA domains in spatially separated compartments of this large particle (Chapter III). In the small subunit processome, the 5\u27 ETS particle forms the base onto which the segregated ribosomal RNA domains are folded. To investigate whether the 5\u27 ETS particle serves as a structural mold for the maturing rRNA domains during earlier assembly stages, we solved the cryo-EM structures of the 5\u27 ETS particle in intermediates preceding the formation of the small subunit processome (Chapter IV). Combined with the in vivo analysis of artificial pre-rRNA fragments, the architecture of the 5\u27 ETS particle shows that the initial steps of ribosome assembly are governed by the functional independence of all rRNA domains and the 5\u27 ETS particle. Completion of ribosomal gene transcription then leads to a conformational change in the 5\u27 ETS particle and small subunit processome formation. In summary, our work provides structural snapshots and biochemical information on more than 50 ribosome assembly factors during different stages of the initiating steps in eukaryotic ribosome biogenesis. These data form the basis for a three-dimensional model of these essential events in the eukaryotic cell
Regulation of Protein Degradation by ADP-Ribosylation
Get PDFProtein quality control is essential for cellular homeostasis. The Ubiquitin-Proteasome System (UPS) is responsible for the regulated breakdown of intracellular proteins. All proteins are not degraded at the same rate in the cell. For instance, global protein turnover rates in mammals change with an average time between 1-2 days. On the other hand, a handful of proteins such as myelin exhibits limited turnover for months or even years. The UPS recycles most of the short-lived proteins in a time range from minutes to days depending on their localization and post-translational modifications. The post-translational modification, poly-ADPribosylation has an estimated half-life of only 1-6 min. My thesis research aimed to reveal how the substrates of Tankyrase are degraded rapidly. Using Drosophila melanogaster, I described the role of Iduna E3 ubiquitin ligase in the regulation of Axin and Tankyrase proteolysis. I found that Iduna controls the proliferation of stem cells in the Drosophila midgut. Using a MS-based approach, I identified lysine 598 as an ADP-ribose acceptor site in Drosophila Tankyrase and showed that TnksK598A adult flies live significantly shorter than control flies. TnksK598A adult flies also reduce their flight, climbing abilities, global protein poly-ADP-ribosylation, and the activation of JNK signaling with age. Furthermore, I demonstrated that the ubcD1 ubiquitin-conjugating enzyme enhances the ubiquitin ligase activity of Iduna. Finally, I proposed a model by which poly-ADP-ribosylation brings together Tankyrase, target proteins, E2 ubiquitin-conjugating enzymes, E3 ubiquitin ligases and 26S proteasomes to accelerate the breakdown of target proteins. My work addresses the general question of how proteins can be rapidly turned over, focusing on the role of Tankyrase-mediated poly-ADP-ribosylation. This work provides novel mechanistic insights into the regulation of protein quality control. Ultimately, these results may be useful to guide the development of new therapies
Who Said That? Towards a Machine-Prediction-Based Approach to Tursiops Truncatus Whistle Localization and Attribution in a Reverberant Dolphinarium
Get PDFDolphin communication research is an active period of growth. Many researchers expect to find significant communicative capacity in dolphins given their known sociality and large and complex brains. Moreover, given dolphins\u27 known acoustic sensitivity, serving their well-studied echolocation ability, some researchers have speculated that dolphin communication is mediated in large part by a sophisticated vocal language. However, evidence supporting this belief is scarce. Among most dolphin species, a particular tonal class of call, termed the whistle, has been identified as socially important. In particular, for the common bottlenose dolphin, Tursiops truncatus – arguably the focal species of most dolphin cognitive and communication research – research has fixated on signature whistles, individually distinctive whistles that seem to convey an individual\u27s identity to conspecifics, can be mimicked, and can be modulated under certain circumstances in ways that may or may not be communicative. Apart from signature whistles, most studies of dolphin calls concern group-based repertoires of whistles and other, pulse-form call types. However, studies of individual repertoires of non-signature whistles, and the phenomenon of combined signature and non-signature vocal exchanges among dolphins, are conspicuously rare in the literature, tending to be limited by either extreme subject confinement or sparse attributions of vocalizer identity. Nevertheless, such studies constitute a logical prerequisite to an understanding of the communicative potential of whistles. This absence can be explained by a methodological limitation in the way in which dolphin sounds are recorded. In particular, no established method exists for recording the whistles of an entire social group of dolphins so as to reliably attribute them to their vocalizers. This thesis proposes a dolphinarium-based system for achieving audio recording with whistle attribution, as well as visual behavioral tracking. Towards achieving the proposed system, I present foundational work involving the installation of permanent hydrophone arrays and cameras in a dolphinarium that enforces strict animal safety regulations. Attributing tonal sounds via the process of sound localization – estimation of a sound\u27s point of origin based on the physical properties of its propagation – in a highly reverberant environment is a notoriously difficult problem, resistant to many conventional signal processing techniques. This thesis will provide evidence of this difficulty, and also a demonstration of a highly e↵ective machine-learning-based solution to the problem. This thesis also provides miscellaneous hardware and the pieces of a computational pipeline towards completion of the full proposed, automated system. Once completed, the proposed system will provide an enormous data stream that will lend itself to large-scale studies of individual repertoires of non-signature whistles and combined signature and non-signature vocal exchanges among an invariant group of socializing dolphins, representing a unique and necessary achievement in dolphin communication research
Jack Quartet and Ariadne Greif, Soprano
No full text2019, May 31
Jack Quartet, string quartet; Ariadne Greif, soprano, performing John Zorn: The Alchemist; Arnold Schoenberg: String Quartet No. 2 for soprano & string quartet in F-sharp Minor, Op. 10.https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1027/thumbnail.jp
Danbi Um, Violin amd Anna Polonsky, Piano
No full text2019, May 24
Danbi Um, violin, Anna Polonsky, piano performed Francesco Geminiani: Sonata in C Minor, Op. 4; Johannes Brahms: Sonata No. 1 in G Major, Op. 78; Alexander Glazunov: Grand Adagio from Raymonda; Fritz Kriesler: Viennese Rhapsodic Fantasietta.https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1028/thumbnail.jp
Lee- Ioniţă-Jokubaviciute Trio
No full text2019, January 25
Mari Lee, violin; Andrei Ioniţă, cello; Ieva Jokubaviciute, piano, performed Debussy: Sonata for Violin and Piano in G Minor, L. 140; Debussy: Sonata for Cello and Piano in D Minor, L. 135; Gliere: Duos for Violin and Cello, Op. 89 (selection); Ravel: Piano Trio in A Minor.https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1044/thumbnail.jp