高级病生noncodingrnaanddisease学习.pptxVIP

Central dogma of biology protein DNA RNA 第1页/共45页 RNA and the genome - the end of the central dogma ~25,000 protein coding genes in humans Protein-coding DNA = 1~2% of genome 第2页/共45页 The number of protein coding genes cannot justify the evolutionary gap between eukaryotes Gene number Transcript number ~25k ~15k ~20k ~6.5k ~31k 30k 30k 第3页/共45页 Increase the complexity by increasing the combinatorial use of exons by alternative splicing primary transcript Alternative splicing Function A Function B 第4页/共45页 ~49k ? ~20k ~23k ~6.5k 30k Gene number Transcript number Still the number of different transcripts cannot justify the evolutionary gap between eukaryotes ~49k 第5页/共45页 The Old Guard Holds steadfast to the idea that most of the transcription (like most of the DNA) is “Junk” Key reasoning: Little sequence conservation of non-coding RNA from species to species Explanation: Transcription of leftover retroviruses and RNA Polymerase infidelity 第6页/共45页 The Old Guard…(holding onto a lack of science) Microarray data of mouse embryonic stem cells identified at least 945 long non-coding RNA’s that are distinctly regulated with development and differentiation. (Dinger, M. E. et al.. Genome Res. 2008, 18:1433–1445 ) Further analysis finds ncRNA to be tissue specific. (Furuno et al. 2006; Kapranov et al. 2002; Nakaya et al. 2007; Ravasi et al. 2006) And, its transcription responds to environmental stimuli. (Cawley et al. 2004; Louro et al. 2007; Ravasi et al. 2006). 第7页/共45页 Continuing… Many have upstream transcriptional binding sites for proteins such as Sp1, c-Myc, p53, and Creb. (Cawley et al. 2004; Euskirchen et al. 2004) Long ncRNA with a known function, such as Xist, have very little sequence similarity. The same miRNA regulates different genes in different species (share little sequence homology/ rapid evolution theory). ….these go on and on…. 第8页/共45页 Eukaryotic RNA transcripts tRNA rRNA snRNA tmRNA Rnase P RNA vRNAs gRNAs MRP RNA SRP RNAs Telomerase RNA Transcripti