TY  - JOUR
A1  - Elkon, Ran
A1  - Loayza-Puch, Fabricio
A1  - Korkmaz, Gozde
A1  - Lopes, Rui
A1  - van Breugel, Pieter C
A1  - Bleijerveld, Onno B
A1  - Altelaar, AF Maarten
A1  - Wolf, Elmar
A1  - Lorenzin, Francesca
A1  - Eilers, Martin
A1  - Agami, Reuven
T1  - Myc coordinates transcription and translation to enhance transformation and suppress invasiveness
JF  - EMBO reports
N2  - c‐Myc is one of the major human proto‐oncogenes and is often associated with tumor aggression and poor clinical outcome. Paradoxically, Myc was also reported as a suppressor of cell motility, invasiveness, and metastasis. Among the direct targets of Myc are many components of the protein synthesis machinery whose induction results in an overall increase in protein synthesis that empowers tumor cell growth. At present, it is largely unknown whether beyond the global enhancement of protein synthesis, Myc activation results in translation modulation of specific genes. Here, we measured Myc‐induced global changes in gene expression at the transcription, translation, and protein levels and uncovered extensive transcript‐specific regulation of protein translation. Particularly, we detected a broad coordination between regulation of transcription and translation upon modulation of Myc activity and showed the connection of these responses to mTOR signaling to enhance oncogenic transformation and to the TGFβ pathway to modulate cell migration and invasiveness. Our results elucidate novel facets of Myc‐induced cellular responses and provide a more comprehensive view of the consequences of its activation in cancer cells.
KW  - c‐Myc
KW  - transcriptional responses
KW  - translational regulation
KW  - transcription
KW  - transformation
KW  - metastasis
KW  - cancer
KW  - protein biosynthesis & quality control
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150373
VL  - 16
IS  - 12
ER  - 
TY  - JOUR
A1  - Benhalevy, Daniel
A1  - Gupta, Sanjay K.
A1  - Danan, Charles H.
A1  - Ghosal, Suman
A1  - Sun, Hong-Wei
A1  - Kazemeier, Hinke G.
A1  - Paeschke, Katrin
A1  - Hafner, Markus
A1  - Juranek, Stefan A.
T1  - The Human CCHC-type Zinc Finger Nucleic Acid-Binding Protein Binds G-Rich Elements in Target mRNA Coding Sequences and Promotes Translation
JF  - Cell Reports
N2  - The CCHC-type zinc finger nucleic acid-binding protein (CNBP/ZNF9) is conserved in eukaryotes and is essential for embryonic development in mammals. It has been implicated in transcriptional, as well as post-transcriptional, gene regulation; however, its nucleic acid ligands and molecular function remain elusive. Here, we use multiple systems-wide approaches to identify CNBP targets and function. We used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify 8,420 CNBP binding sites on 4,178 mRNAs. CNBP preferentially bound G-rich elements in the target mRNA coding sequences, most of which were previously found to form G-quadruplex and other stable structures in vitro. Functional analyses, including RNA sequencing, ribosome profiling, and quantitative mass spectrometry, revealed that CNBP binding did not influence target mRNA abundance but rather increased their translational efficiency. Considering that CNBP binding prevented G-quadruplex structure formation in vitro, we hypothesize that CNBP is supporting translation by resolving stable structures on mRNAs.
KW  - PAR-CLIP
KW  - ribosome profiling
KW  - translational regulation
KW  - posttranscriptional gene regulation
KW  - zinc-finger
KW  - RNA binding protein
KW  - CLIP-seq
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171122
VL  - 18
IS  - 12
ER  -