Dr. Marcel Dinger, PhD discusses some of the most recent findings that shed light on non-coding RNAs in the genome. **this webinar is no longer available**
Abstract
Approximately 98% of the human genome comprises noncoding DNA, the function
of which is largely unknown. Intriguingly, more than 85% of single nucleotide polymorphisms identified to be associated with disease in genome-wide studies (GWAS) occur within noncoding regions, suggesting that examining the role of these regions of the genome will be important for understanding and potentially treating disease.
The relatively recent discovery of widespread transcription of potentially functional long noncoding RNAs (lncRNAs) from the mammalian genome [1] led us to investigate whether or not GWAS hits in noncoding regions could be reconciled by the transcription of regulatory RNAs from these loci. As described by our lab and others, lncRNAs typically show highly developmental-stage- and tissue-specific expression [2,3], and therefore cannot be easily detected by conventional RNA-Seq,
which requires exponentially greater depth to detect increasingly rare transcripts.
To overcome this problem, we recently developed a technique we term RNA-Capture-Seq, which combines custom capture tiling arrays with RNA sequencing to target
transcription arising from specific areas of the genome [4].
We have now used this approach to target 77 chromosomal regions identified by GWAS. Using RNA pooled from diverse human tissues, we identify novel transcripts, totalling hundreds, associated with the majority of the targeted regions. To further realise the potential of the method to understand specific diseases, we have designed further capture arrays to target GWAS regions linked to specific diseases, including endometriosis and melanoma.
For these experiments, RNA from biologically relevant normal and disease tissues were used to look for novel transcripts. As a result, we have identified numerous new lncRNAs whose expression appears to be specifically associated with disease and arise from disease-associated regions.
Although functional investigation of these transcripts is still underway, we propose that the results of these experiments bring an intriguing new perspective into our understanding of how information in the genome is encoded and has considerable potential to identify novel regulators, which may prove valuable as biomarkers and therapeutic targets, involved in disease and development.
- Mercer TR, Dinger ME, Mattick JS (2009) Long noncoding RNAs: insights into function. Nat Rev Genet 10: 155-159. [*equal contribution]
- Dinger ME, Amaral PP, Mercer TR, Pang KC, Bruce SJ, et al. (2008) Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res 18: 1433-1445. [equal contribution]
- Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS (2008) Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci U S A 105: 716-721. [*equal contribution]
- Mercer TR, Dinger ME, Gerhardt DJ, Crawford J, Trapnell C, et al. (2011)