(精选)Novel regulators of gene expression and genome integrity教学课件.pptVIP

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(精选)Novel regulators of gene expression and genome integrity教学课件.ppt

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演示文稿演讲PPT学习教学课件医学文件教学培训课件

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * tRNA-DERIVED SMALL RNAs - A new family of regulatory small RNAs? - Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs COLE C., et al. RNA (2009) Deep sequencing revealed that 5’ halves from tRNAs was the most abundant small RNA population The tRNAs are almost exclusively processed from the 5’ end with cleavage by Dicer at the D-loop resulting in the generation of ~19 nt-long fragments Increased levels of tRNAs might force Dicer to accept tRNAs as substrate (modulation of miRNA biogenesis?) In HeLa cells the most abundant small tRNAs were derived from tRNALys, tRNAVal, tRNAGln and tRNAArg Deep sequencing revealed that 5’ halves from tRNAs was the most abundant small RNA population Hidden layers of human small RNAs Kawaji, H. et al. BMC Genomics 2008, 9:157 ~ 21 nt ~ 32 nt Dicer Angiogenin Are miRNA and small tRNA pathways connected? - Small tRNAs vs microRNAs - tRNA-DERIVED SMALL RNAs - A new family of regulators small RNAs? - THE tRNase Z FAMILY OF PROTEINS Precise trimming and processing of precursor tRNA molecules requires: removal of the 5’ leader sequences by the ubiquitous enzyme RNase P removal of the 3’ trailer sequences by tRNase Z the modification of tRNA nucleotides intron removal EXTERNAL GUIDE SEQUENCES (EGS) TARGET TrzL CLEAVAGE tRNase ZL can cleave any target RNA at any desired site by recognizing a pre-tRNA-like or micro-pre-tRNA-like complex formed between the target RNA and small guide or external guide sequence RNA (sgRNA). piRNA-like ncRNAs co-immunoprecipitate with human tRNase ZL 5’-half-tRNAGlu was predominant Genuine targets of tRNase ZL-guided by 5’-half-tRNAGlu revealed by microarrays p53 SIGNALING PATHWAYS Genuine targets of tRNase ZL-guided by 5’-half-tRNAGlu revealed by microarrays APOPTOTIC PATHWAYS miRNAs CAN BE USED BY tRNase Z AS GUIDES TO TARGET mRNAS Human cytosolic tRNase ZL can downregulate gene