@article{DoerkPeterlongoMannermaaetal.2019,
  author    = {D{\"o}rk, Thilo and Peterlongo, Peter and Mannermaa, Arto and Bolla, Manjeet K. and Wang, Qin and Dennis, Joe and Ahearn, Thomas and Andrulis, Irene L. and Anton-Culver, Hoda and Arndt, Volker and Aronson, Kristan J. and Augustinsson, Annelie and Beane Freeman, Laura E. and Beckmann, Matthias W. and Beeghly-Fadiel, Alicia and Behrens, Sabine and Bermisheva, Marina and Blomqvist, Carl and Bogdanova, Natalia V. and Bojesen, Stig E. and Brauch, Hiltrud and Brenner, Hermann and Burwinkel, Barbara and Canzian, Federico and Chan, Tsun L. and Chang-Claude, Jenny and Chanock, Stephen J. and Choi, Ji-Yeob and Christiansen, Hans and Clarke, Christine L. and Couch, Fergus J. and Czene, Kamila and Daly, Mary B. and dos-Santos-Silva, Isabel and Dwek, Miriam and Eccles, Diana M. and Ekici, Arif B. and Eriksson, Mikael and Evans, D. Gareth and Fasching, Peter A. and Figueroa, Jonine and Flyger, Henrik and Fritschi, Lin and Gabrielson, Marike and Gago-Dominguez, Manuela and Gao, Chi and Gapstur, Susan M. and Garc{\´i}a-Closas, Montserrat and Garc{\´i}a-S{\´a}enz, Jos{\´e} A. and Gaudet, Mia M. and Giles, Graham G. and Goldberg, Mark S. and Goldgar, David E. and Guen{\´e}l, Pascal and Haeberle, Lothar and Haimann, Christopher A. and H{\aa}kansson, Niclas and Hall, Per and Hamann, Ute and Hartman, Mikael and Hauke, Jan and Hein, Alexander and Hillemanns, Peter and Hogervorst, Frans B. L. and Hooning, Maartje J. and Hopper, John L. and Howell, Tony and Huo, Dezheng and Ito, Hidemi and Iwasaki, Motoki and Jakubowska, Anna and Janni, Wolfgang and John, Esther M. and Jung, Audrey and Kaaks, Rudolf and Kang, Daehee and Kapoor, Pooja Middha and Khusnutdinova, Elza and Kim, Sung-Won and Kitahara, Cari M. and Koutros, Stella and Kraft, Peter and Kristensen, Vessela N. and Kwong, Ava and Lambrechts, Diether and Le Marchand, Loic and Li, Jingmei and Lindstr{\"o}m, Sara and Linet, Martha and Lo, Wing-Yee and Long, Jirong and Lophatananon, Artitaya and Lubiński, Jan and Manoochehri, Mehdi and Manoukian, Siranoush and Margolin, Sara and Martinez, Elena and Matsuo, Keitaro and Mavroudis, Dimitris and Meindl, Alfons and Menon, Usha and Milne, Roger L. and Mohd Taib, Nur Aishah and Muir, Kenneth and Mulligan, Anna Marie and Neuhausen, Susan L. and Nevanlinna, Heli and Neven, Patrick and Newman, William G. and Offit, Kenneth and Olopade, Olufunmilayo I. and Olshan, Andrew F. and Olson, Janet E. and Olsson, H{\aa}kan and Park, Sue K. and Park-Simon, Tjoung-Won and Peto, Julian and Plaseska-Karanfilska, Dijana and Pohl-Rescigno, Esther and Presneau, Nadege and Rack, Brigitte and Radice, Paolo and Rashid, Muhammad U. and Rennert, Gad and Rennert, Hedy S. and Romero, Atocha and Ruebner, Matthias and Saloustros, Emmanouil and Schmidt, Marjanka K. and Schmutzler, Rita K. and Schneider, Michael O. and Schoemaker, Minouk J. and Scott, Christopher and Shen, Chen-Yang and Shu, Xiao-Ou and Simard, Jaques and Slager, Susan and Smichkoska, Snezhana and Southey, Melissa C. and Spinelli, John J. and Stone, Jennifer and Surowy, Harald and Swerdlow, Anthony J. and Tamimi, Rulla M. and Tapper, William J. and Teo, Soo H. and Terry, Mary Beth and Toland, Amanda E. and Tollenaar, Rob A. E. M. and Torres, Diana and Torres-Mej{\´i}a, Gabriela and Troester, Melissa A. and Truong, Th{\´e}r{\`e}se and Tsugane, Shoichiro and Untch, Michael and Vachon, Celine M. and van den Ouweland, Ans M. W. and van Veen, Elke M. and Vijai, Joseph and Wendt, Camilla and Wolk, Alicja and Yu, Jyh-Cherng and Zheng, Wei and Ziogas, Argyrios and Ziv, Elad and Dunnig, Alison and Pharaoh, Paul D. P. and Schindler, Detlev and Devilee, Peter and Easton, Douglas F.},
  title     = {Two truncating variants in FANCC and breast cancer risk},
  series = {Scientific Reports},
  volume    = {9},
  journal   = {Scientific Reports},
  organization    = {ABCTB Investigators, NBCS Collaborators},
  doi       = {10.1038/s41598-019-48804-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222838},
  year      = {2019},
  abstract  = {Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95\%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.},
  language  = {en}
}
@phdthesis{Santos2021,
  author    = {Santos, Sara F. C.},
  title     = {Expanding the targetome of Salmonella small RNA PinT using MS2 affinity purification and RNA-Seq (MAPS)},
  doi       = {10.25972/OPUS-20492},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204926},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Bacterial small RNAs are key mediators of post-transcriptional gene regulation. An increasing number of sRNAs have been implicated in the regulation of virulence programs of pathogenic bacteria. Recently, in the enteric pathogen Salmonella Typhimurium, the PinT sRNA has gained increased importance as it is the most upregulated sRNA as Salmonella infects mammalian host cells (Westermann et al., 2016). PinT acts as a temporal regulator of Salmonella's two major pathogenicity islands, SPI-1 and SPI-2 (Kim et al., 2019; Westermann et al., 2016). However, the complete set of PinT targets, its role in Salmonella infection and host response is not yet fully understood. Building on the MS2 affinity purification and RNA- seq (MAPS) method (Lalaouna et al., 2015), we here set out to globally identify direct RNA ligands of PinT, relevant to Salmonella infection. We transferred the classical MAPS technique, based on sRNA-bait overexpression, to more physiological conditions, using endogenous levels of the sRNA. Making the henceforth identified targets, less likely to represent artefacts of the overexpression. More importantly, we progressed the MAPS technique to in vivo settings and by doing so, we were able pull-down bacterial RNA transcripts bound by PinT during macrophage infection. While we validate previously known PinT targets, our integrated data revealed novel virulence relevant target. These included mRNAs for the SPI-2 effector SteC, the PhoQ activator UgtL and the 30S ribosomal protein S22 RpsV. Next, we follow up on SteC, the best characterized virulence relevant PinT target. Using genetic and biochemical assays, we demonstrate that PinT represses steC mRNA by direct base-pairing and translational interference. PinT-mediated regulation of SteC leads to alterations in the host response to Salmonella infection. This regulation impacts the cytokine response of infected macrophages, by altering IL10 production, and possibly driving the macrophages to an anti-inflammatory state, more permise to infection. SteC is responsible for F-actin meshwork rearrangements around the SCV (Poh et al., 2008). Here we demonstrate that PinT-mediated regulation of SteC, impacts the formation of this actin meshwork in infected cells. Our results demonstrate that SteC expression is very tightly regulated by PinT in two layers; indirectly, by repressing ssrB and crp; and directly by binding to steC 5'UTR. PinT contributes to post-transcriptional cross-talk between invasion and intracellular replication programs of Salmonella, by controlling the expression of both SPI-1 and SPI-2 genes (directly and indirectly). Together, our collective data makes PinT the first sRNA in Gram-negatives with a pervasive role in virulence, at the center of Salmonella virulence programs and provide molecular input that could help explain the attenuation of pinT-deficient Salmonella strains in whole animal models of infection.},
  language  = {en}
}