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Series GSE105082 Query DataSets for GSE105082
Status Public on Apr 30, 2018
Title RNA G-quadruplexes mark repressive upstream open reading frames in human mRNAs
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Other
Summary Translational control is a key determinant of protein abundance, which in turns defines the physiology and pathology of human cells. Initiation of translation is highly regulated in eukaryotes and is considered as the rate-limiting step of protein synthesis. mRNA secondary structures in 5’ untranslated region (UTR) and associated helicases have been characterised as key determinants of translation initiation. Nevertheless the transcriptome-wide contribution of non-canonical secondary structures, such as RNA G-quadruplexes (rG4s), to the translation of human mRNAs remains largely unappreciated. Here we use a ribosome profiling strategy to investigate the translational landscape associated to rG4s-containing mRNAs and the contribution of two rG4s-specialised DExH-box helicases, DHX9 and DHX36, to translation initiation in human cells. We show that rG4-forming sequences in 5’-UTR is associated with decreased translation efficiency which correlate with an increased ribosome density within the 5’-UTRs. We found that rG4s contribute to the translation of upstream open reading frames, and as a consequence, thwart the translation of the associated protein coding sequences (CDS). Depletion of the DHX36 and DHX9 helicases demonstrated that the formation of the rG4 structural motif rather than its nucleotide sequence mediate translation initiation. Our findings unveil a role for non-canonical structures in defining alternative 5’ starts for human mRNAs translation initiation.
 
Overall design 11 Ribo-Seq and RNA-Seq matched samples; 1 iCLIP libraries containing two barcoded replicates
 
Contributor(s) Murat P, Marsico G, Herdy B, Ghanbarian A, Portella G, Balasubramanian S
Citation(s) 30591072
Submission date Oct 17, 2017
Last update date May 15, 2019
Contact name Giovanni Marsico
E-mail(s) persego@gmail.com
Organization name CRUK Cambridge Institute
Street address Robinson Way
City Cambridge
ZIP/Postal code CB2 0RE
Country United Kingdom
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (24)
GSM2817677 iCLIP-DHX9-1
GSM2817678 iCLIP-DHX9-2
GSM2817679 RPF-NT-1
Relations
BioProject PRJNA414611
SRA SRP120157

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Supplementary file Size Download File type/resource
GSE105082_RAW.tar 25.5 Mb (http)(custom) TAR (of BW, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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