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microRNAs : genome regulators

microRNAs : genome regulators. Aizhan Bizhanova. Overview. miRNA What are miRNAs ? Function and role C.elegans Role of miRNAs in developmental genetics of C.elegans lin-4 miRNA , “precocious” and “retarded” phenotypes Drosophila let-7 miRNA affects neuronal cell differentiation?.

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microRNAs : genome regulators

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  1. microRNAs: genome regulators AizhanBizhanova

  2. Overview • miRNA • What are miRNAs? • Function and role • C.elegans • Role of miRNAs in developmental genetics of C.elegans • lin-4 miRNA, “precocious” and “retarded” phenotypes • Drosophila • let-7 miRNA affects neuronal cell differentiation?

  3. miRNA • microRNAs (miRNAs) are single-stranded non-coding RNAs, 21-23 nt long. • Discovered by 1993 by Victor Ambros, Rosalind Lee and Rhonda Feinbaum during a study of the gene lin-14 in C. elegansdevelopment • miRNAs regulate their target genes by base pairing with 3’ UTR of mRNA • 3’ Untranslated Region is a protein binding site in mRNA that is not translated • miRNAs bind with their “seed regions” (nucleotides 2-7) to the 3’ UTR of their target mRNA via base complementarity

  4. Making miRNAs 1.Transcribing the primary miRNA (pri-miRNA) • RNA is capped and poly-adenylated • Specific stem-loop structures form 2. Nuclear processing of pri-miRNA • Drosha/Pasha complex cleaves out the base of the stem-loop structure, releasing the pre-miRNA 3. Export of pre-miRNA from the nucleus to the cytoplasm by Exportin5 4. Cytoplasmic processing of pre-miRNA • Dicer cleaves the “loop” portion to form the miRNA duplex 5.Loading of miRNA duplex into RISC 6.Strand selection 7.RISC activation 8.miRNA-RISC activity

  5. miRNAs: role and function • Human genome has about 200-300 miRNA genes (1% of the protein coding genes) • Shared miRNA sites in different animal genomes- homologous miRNA putative targets? • Base pair with sites in the 3’ UTR of their target mRNAs. The seed sequence at the 5’ end of miRNA determines the specificity of miRNA-target RNA interactions. • Downregulate the expression of target proteins • Play an important role in development, cellular differentiation, proliferation, oncogenesis and apoptosis, etc.

  6. Mode of Action of miRNAs in Plants and Animals http://www.ambion.com/techlib/resources/miRNA/mirna_fun.html

  7. C.elegans

  8. lin-4: the first discovered miRNA • Heterochronic genes control developmental timing • lin-4miRNA is a heterochronic gene lin-14 • lin-4 lin-28 Vella and Slack, 2005

  9. let-7 : cell fate “determinant”? abrupt broad clockwork orange chinmo • Ecdysone? broad? let-7-C Taken from Sokol, presentation Zhu, 2006

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