@article{SchwarzLukassenBhandareetal.2022,
  author    = {Schwarz, Jessica Denise and Lukassen, S{\"o}ren and Bhandare, Pranjali and Eing, Lorenz and Snaebj{\"o}rnsson, Marteinn Thor and Garc{\´i}a, Yiliam Cruz and Kisker, Jan Philipp and Schulze, Almut and Wolf, Elmar},
  title     = {The glycolytic enzyme ALDOA and the exon junction complex protein RBM8A are regulators of ribosomal biogenesis},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {10},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2022.954358},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290875},
  year      = {2022},
  abstract  = {Cellular growth is a fundamental process of life and must be precisely controlled in multicellular organisms. Growth is crucially controlled by the number of functional ribosomes available in cells. The production of new ribosomes depends critically on the activity of RNA polymerase (RNAP) II in addition to the activity of RNAP I and III, which produce ribosomal RNAs. Indeed, the expression of both, ribosomal proteins and proteins required for ribosome assembly (ribosomal biogenesis factors), is considered rate-limiting for ribosome synthesis. Here, we used genetic screening to identify novel transcriptional regulators of cell growth genes by fusing promoters from a ribosomal protein gene (Rpl18) and from a ribosomal biogenesis factor (Fbl) with fluorescent protein genes (RFP, GFP) as reporters. Subsequently, both reporters were stably integrated into immortalized mouse fibroblasts, which were then transduced with a genome-wide sgRNA-CRISPR knockout library. Subsequently, cells with altered reporter activity were isolated by FACS and the causative sgRNAs were identified. Interestingly, we identified two novel regulators of growth genes. Firstly, the exon junction complex protein RBM8A controls transcript levels of the intronless reporters used here. By acute depletion of RBM8A protein using the auxin degron system combined with the genome-wide analysis of nascent transcription, we showed that RBM8A is an important global regulator of ribosomal protein transcripts. Secondly, we unexpectedly observed that the glycolytic enzyme aldolase A (ALDOA) regulates the expression of ribosomal biogenesis factors. Consistent with published observations that a fraction of this protein is located in the nucleus, this may be a mechanism linking transcription of growth genes to metabolic processes and possibly to metabolite availability.},
  language  = {en}
}
@article{TrifaultMamontovaCossaetal.2024,
  author    = {Trifault, Barbara and Mamontova, Victoria and Cossa, Giacomo and Ganskih, Sabina and Wei, Yuanjie and Hofstetter, Julia and Bhandare, Pranjali and Baluapuri, Apoorva and Nieto, Blanca and Solvie, Daniel and Ade, Carsten P. and Gallant, Peter and Wolf, Elmar and Larsen, Dorthe H. and Munschauer, Mathias and Burger, Kaspar},
  title     = {Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts},
  series = {Nucleic Acids Research},
  volume    = {52},
  journal   = {Nucleic Acids Research},
  number    = {6},
  doi       = {10.1093/nar/gkae022},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350208},
  pages     = {3050-3068},
  year      = {2024},
  abstract  = {RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54\(^{nrb}\) marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood. Here we show that the topoisomerase II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-inducible antisense intergenic non-coding RNA (asincRNA) in human cancer cells. Such transcripts originate from distinct nucleolar intergenic spacer regions and form DNA-RNA hybrids to tether NONO to the nucleolus in an RNA recognition motif 1 domain-dependent manner. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of a subset of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signalling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.},
  language  = {en}
}
@article{BaluapuriHofstetterDudvarskiStankovicetal.2019,
  author    = {Baluapuri, Apoorva and Hofstetter, Julia and Dudvarski Stankovic, Nevenka and Endres, Theresa and Bhandare, Pranjali and Vos, Seychelle Monique and Adhikari, Bikash and Schwarz, Jessica Denise and Narain, Ashwin and Vogt, Markus and Wang, Shuang-Yan and D{\"u}ster, Robert and Jung, Lisa Anna and Vanselow, Jens Thorsten and Wiegering, Armin and Geyer, Matthias and Maric, Hans Michael and Gallant, Peter and Walz, Susanne and Schlosser, Andreas and Cramer, Patrick and Eilers, Martin and Wolf, Elmar},
  title     = {MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation},
  series = {Molecular Cell},
  volume    = {74},
  journal   = {Molecular Cell},
  doi       = {10.1016/j.molcel.2019.02.031},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221438},
  pages     = {674-687},
  year      = {2019},
  abstract  = {The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and enhances RNA polymerase II (Pol II) function, but its precise mode of action is poorly understood. Using mass spectrometry of both MYC and Pol II complexes, we show here that MYC controls the assembly of Pol II with a small set of transcription elongation factors that includes SPT5, a subunit of the elongation factor DSIF. MYC directly binds SPT5, recruits SPT5 to promoters, and enables the CDK7-dependent transfer of SPT5 onto Pol II. Consistent with known functions of SPT5, MYC is required for fast and processive transcription elongation. Intriguingly, the high levels of MYC that are expressed in tumors sequester SPT5 into non-functional complexes, thereby decreasing the expression of growth-suppressive genes. Altogether, these results argue that MYC controls the productive assembly of processive Pol II elongation complexes and provide insight into how oncogenic levels of MYC permit uncontrolled cellular growth.},
  language  = {en}
}