TY  - JOUR
A1  - Whisnant, Adam W.
A1  - Jürges, Christopher S.
A1  - Hennig, Thomas
A1  - Wyler, Emanuel
A1  - Prusty, Bhupesh
A1  - Rutkowski, Andrzej J.
A1  - L'hernault, Anne
A1  - Djakovic, Lara
A1  - Göbel, Margarete
A1  - Döring, Kristina
A1  - Menegatti, Jennifer
A1  - Antrobus, Robin
A1  - Matheson, Nicholas J.
A1  - Künzig, Florian W. H.
A1  - Mastrobuoni, Guido
A1  - Bielow, Chris
A1  - Kempa, Stefan
A1  - Liang, Chunguang
A1  - Dandekar, Thomas
A1  - Zimmer, Ralf
A1  - Landthaler, Markus
A1  - Grässer, Friedrich
A1  - Lehner, Paul J.
A1  - Friedel, Caroline C.
A1  - Erhard, Florian
A1  - Dölken, Lars
T1  - Integrative functional genomics decodes herpes simplex virus 1
JF  - Nature Communications
N2  - The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution. Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.
KW  - infected-cell protein
KW  - messenger RNA
KW  - binding protein
KW  - type 1
KW  - identification
KW  - ICP27
KW  - translation
KW  - expression
KW  - sequence
KW  - domain
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229884
VL  - 11
ER  - 
TY  - JOUR
A1  - Bensaad, Karim
A1  - Favaro, Elena
A1  - Lewis, Caroline A.
A1  - Peck, Barrie
A1  - Lord, Simon
A1  - Collins, Jennifer M.
A1  - Pinnick, Katherine E.
A1  - Wigfield, Simon
A1  - Buffa, Francesca M.
A1  - Li, Ji-Liang
A1  - Zhang, Qifeng
A1  - Wakelam, Michael J. O.
A1  - Karpe, Fredrik
A1  - Schulze, Almut
A1  - Harris, Adrian L.
T1  - Fatty Acid Uptake and Lipid Storage Induced by HIF-1 alpha Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation
JF  - Cell Reports
N2  - An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1 alpha (HIF-1 alpha)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O-2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via beta-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo.
KW  - inducible factor-I
KW  - binding protein
KW  - triglyceride accumulation
KW  - cancer cell
KW  - complex-III
KW  - beta-oxidation
KW  - metabolism
KW  - lipogenesis
KW  - proliferation
KW  - resistance
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115162
SN  - 2211-1247
VL  - 9
IS  - 1
ER  -