TY  - JOUR
A1  - Sauer, Markus
A1  - Juranek, Stefan A.
A1  - Marks, James
A1  - De Magis, Alessio
A1  - Kazemier, Hinke G
A1  - Hilbig, Daniel
A1  - Benhalevy, Daniel
A1  - Wang, Xiantao
A1  - Hafner, Markus
A1  - Paeschke, Katrin
T1  - DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions
JF  - Nature Communications
N2  - Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36 targets and function is lacking. We map globally DHX36 binding to RNA in human cell lines and find it preferentially interacting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36 knockout (KO) results in a significant increase in target mRNA abundance, ribosome occupancy and protein output from these targets decrease, suggesting that they were rendered translationally incompetent. Considering that DHX36 targets, harboring G4s, preferentially localize in stress granules, and that DHX36 KO results in increased SG formation and protein kinase R (PKR/EIF2AK2) phosphorylation, we speculate that DHX36 is involved in resolution of rG4 induced cellular stress.
KW  - RNA metabolism
KW  - Translation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227486
VL  - 10
IS  - 2421
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  -