(精选)microRNA’s Computational biology seminar教学课件.pptVIP

micro RNA’s Computational biology seminar  Ariel Jaimovich November 17th 2005 The central dogma of biology This is not always the case: First ‘life forms’ viruses Transcription RNA Translation Protein Dioxy ribo @#$%##@?! Rna performs many functions Ribosomes tRNA Nuclear detaining RNAi Micro RNA ~22nt rna Precursor stem loop Post-transcription regulation miRNA History Lin-4 inhibits LIN14, but no LIN 4 protein was found (1993) miRNA appear in many organisms Highly conserved, many ‘copies’ in each organism 4 paralogs of let7 4 in c elegans 15 in human 1 in drosophila Plants Vs Animals miRNA - function Sequence recognition Positions 2-8 are most important How do we know Why ? Base pairing ? Function How do we know which process is active ? Protein coding rna 3’ utr Function (cont) Plants vs animals Number of target seq. on 3’ utr ? Some miRNA target the same mRNA in different sites siRNA vs miRNA Genomic origin – miRNA from genes siRNA from mRNAs, transposons, viruses... Synthesis One siRNA duplex ? many siRNA Conservation miRNA vs siRNA miRNA in plants Near-perfect complementarity mRNA cleavage, usually of TF’s related to developmental processes Conservation between Arabidopsis and rice Defend against viruses miRNA in animals mRNA cleavage or translational silencing Conservation is also high (?) Different numbers of paralogs Identification of hundreds of conserved and nonconserved human microRNAs Isaac Bentwich, Amir Avniel, Yael Karov, Ranit Aharonov Shlomit Gilad, Omer Barad, Adi Barzilai, Paz Einat, Uri Einav, Eti Meiri, Eilon Sharon, Yael Spector ?Zvi Bentwich Nature genetics - June 2005 Goal Find new human micro RNAs Motivation Current gene search techniques: Hairpins Conservation Try to search with a wider scope Search algorithm Fold the genome ~ 11 milion hairpins Prediction (1) Magic box ~ 430,000 hairpins Structure features Hairpin length Loop length Stability score Free energy per nucleotide Matching pairs Bulge size Magic b