功能基因组学重大疾病中非编码rna调控分析.ppt

* For mRNAs-mRNAs cis-correlations, the proportion of proximal 20 kb extreme correlations is less important * it omitted many singleton transcripts and non-polyadenylated?transcripts (tiling array?data shows more than 40% of transcripts are non-polyadenylated) (Cheng 2005). * 功能 信号分子（signal molecule）、诱饵分子(decoy molecule)、引导分子（guide molecule）、骨架分子（scaffold molecule） lncRNA are mostly polII transcribed, and has similar histone mark profiles as protein-coding genes. * 核旁斑(nuclear paraspeckle)为存在于细胞核内的独立的核糖核蛋白小体, 其功能并未被完全阐释, 但该结构已被证实在mRNA 剪切、加工及储留中发挥重要功能.. lncRNAs 对于核旁斑的形成及其结构的完整性是必需的, Figure?1.?Cellular functions of long ncRNAs. LncRNAs can act in diverse ways in the cell. In general, they can regulate gene expression, influence protein localization (D) and are important for the formation of cellular substructures or protein complexes, where they fulfill scaffolding functions (C; H).199?Regulating gene expression is one of the best studied functions of lncRNA and multiple mechanisms are applied by lncRNAs. (A) LncRNAs coul be processed into small, single- or double-stranded RNAs that could act as endo-siRNAs targeting other RNAs, which subsequently leads to target degradation. (B) LncRNAs can act as “miRNA sponge” and sequester miRNAs to inactivate these small regulatory RNAs. This influences the expression of miRNA target genes.200?(D) The interaction of lncRNAs with proteins they can modulate protein activity and localization. For example, the lncRNA NRON (non-coding repressor of NFAT) binds to the cellular transcription factor NFAT (nuclear factor of activated T cells). This regulates nuclear-cytoplasmic trafficking of NFAT and finally leading to an repression of NFAT target gene expression.201?(E) Furthermore, lncRNA regulate gene transcription via recruiting transcription factors to their target gene promoters, therefore activating gene expression.39?However, they can also block binding of general transcription factors, potentially via formation of RNA-DNA-Tripl