Transposable elements are viewed as ‘selfish genetic elements’, yet they contribute to gene regulation and genome evolution in diverse ways. More than half of the human genome consists of transposable elements. With over 1 million insertions, Alu elements belong to the short interspersed nuclear element (SINE) family of repetitive elements, and with over 1 million insertions they make up more than 10% of the human genome. Despite their abundance and the potential evolutionary advantages they confer, Alu elements can be mutagenic to the host as they can act as splice acceptors, inhibit translation of mRNAs and cause genomic instability. Alu elements are the main targets of the RNA-editing enzyme ADAR and the formation of Alu exons is suppressed by the nuclear ribonucleoprotein HNRNPC, but the broad effect of massive secondary structures formed by inverted-repeat Alu elements on RNA processing in the nucleus remains unknown.
More...Transposable elements are viewed as ‘selfish genetic elements’, yet they contribute to gene regulation and genome evolution in diverse ways. More than half of the human genome consists of transposable elements. With over 1 million insertions, Alu elements belong to the short interspersed nuclear element (SINE) family of repetitive elements, and with over 1 million insertions they make up more than 10% of the human genome. Despite their abundance and the potential evolutionary advantages they confer, Alu elements can be mutagenic to the host as they can act as splice acceptors, inhibit translation of mRNAs and cause genomic instability. Alu elements are the main targets of the RNA-editing enzyme ADAR and the formation of Alu exons is suppressed by the nuclear ribonucleoprotein HNRNPC, but the broad effect of massive secondary structures formed by inverted-repeat Alu elements on RNA processing in the nucleus remains unknown. Here we show that DHX9, an abundant nuclear RNA helicase, binds specifically to inverted-repeat Alu elements that are transcribed as parts of genes. Loss of DHX9 leads to an increase in the number and amount of circular RNAs, translational repression of reporters containing inverted-repeat Alu elements, and transcriptional rewiring (the creation of mostly nonsensical novel connections between exons) of susceptible loci. Biochemical purifications of DHX9 identify the interferon-inducible isoform of ADAR (p150), but not the constitutively expressed ADAR isoform (p110), as an RNA-independent interaction partner. Co-depletion of ADAR and DHX9 augments the double-stranded RNA accumulation defects, leading to higher levels of circular RNA production, revealing a functional link between these two enzymes. Our work uncovers an evolutionarily conserved function of DHX9. We propose that it acts as a nuclear RNA resolvase that neutralizes the immediate threat posed by transposon insertions and allows these elements to evolve as tools for the post-transcriptional regulation of gene expression.
This SuperSeries is composed of the SubSeries listed below.
Overall design: Refer to individual Series
Less...| Accession | PRJNA336358; GEO: GSE85164 |
| Type | Umbrella project |
| Publications | Aktaş T et al., "DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome.", Nature, 2017 Apr 6;544(7648):115-119 |
| Submission | Registration date: 3-Aug-2016
Akhtar Lab, Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics |
| Relevance | Superseries |
Project Data:
| Resource Name | Number
of Links |
|---|
| Sequence data |
| SRA Experiments | 94 |
| Publications |
| PubMed | 1 |
| Other datasets |
| BioSample | 94 |
| GEO DataSets | 7 |
DHX9 suppresses spurious RNA processing defects originating from the Alu invasion of the human genome encompasses the following 6 sub-projects:
| Project Type | Number of Projects |
| Other | 4 |
BioProject
accession | Name | Title |
|---|
| PRJNA336351 | DHX9 suppresses spurious RNA processing defects originating from the Alu invasion of the human genome [uvCLAP CLIP-seq] | DHX9 suppresses spurious RNA processing defects originating from the Alu invasion of the human genome [uvCLAP CLIP-seq] (Akhtar Lab, Chromatin Regulation,...) | | PRJNA374033 | Homo sapiens | DHX9 suppresses spurious RNA processing defects originating from the Alu invasion of the human genome [hnRNPC FLASH CLIP-seq] (Akhtar Lab, Chromatin Regulation,...) | | PRJNA352685 | Mus musculus | DHX9 suppresses spurious RNA processing defects originating from the Alu invasion of the human genome [XL9 DHX9 FLASH CLIP-seq] (Akhtar Lab, Chromatin Regulation,...) | | PRJNA353095 | Mus musculus | DHX9 suppresses spurious RNA processing defects originating from the Alu invasion of the human genome [XL8 DHX9 FLASH CLIP-seq] (Akhtar Lab, Chromatin Regulation,...) |
|
| Transcriptome or Gene expression | 2 |
BioProject
accession | Organism | Title |
|---|
| PRJNA336449 | Homo sapiens | DHX9 suppresses spurious RNA processing defects originating from the Alu invasion of the human genome [RNA-Seq] (Akhtar Lab, Chromatin Regulation,...) | | PRJNA351228 | Homo sapiens | DHX9 suppresses spurious RNA processing defects originating from the Alu invasion of the human genome [XL1 DHX9 FLASH CLIP-seq] (Akhtar Lab, Chromatin Regulation,...) |
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