MicroRNA (miRNA)

miRNA biogenesis
miRNA biogenesis
  • mediates RNAi in an endogenous manner
  • 21 – 25 nucleotide small RNA
  • non-coding
  • binds to the 3′-UTR of target mRNA.
  • miRNA genes may be located within introns and exons of other (protein-coding or non-coding) genes.
    • In these cases, miRNA genes may be transcriptionally regulated through the promoters of these genes.
  • MicroRNA genes are first transcribed into primary miRNA (pri-miRNA), which is further processed to pre-miRNA.
    • pre-miRNA is exported to the cytoplasm, where it is cleaved by the Dicer enzyme into shorter RNA molecules called imperfect miRNA (miRNA*).
    • miRNA* is separated into single strand RNA molecules, from which usually one (guide strand) acts as the final mature miRNA, that interacts with the target mRNA.
  • If miRNA binds partial complementary, translation is inhibited.
  • If miRNA binds full complementary, target mRNA is degraded.
  • MicroRNA function in general seems to be linked to multicellularity:
    • Stem cells don’t need functional miRNAs for viability, but they fail to differentiate without miRNAs.
    • miRNAs are essential for vertebrate development.
    • miRNAs are involved in differentiation and maintenance of cell identity.
  • Examples
    • miR-143 and miR-145 expression is downregulated in various human cell lines derived from breast, prostate, cervical, lymphoid cancers, and, particularly, colorectal tumors.
    • Predicted targets for the miR-17-92 cluster include tumor suppressor genes PTEN and RB2.

Refernces:

  1. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nature reviews. Genetics. 2004;5(7):522-31. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15211354.
  2. Wienholds E, Plasterk RH. MicroRNA function in animal development. FEBS letters. 2005;579(26):5911-22. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16111679.
  3. Michael MZ, O’Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microR-NAs in colorectal neoplasia. Molecular Cancer Research. 2003;1(12):882–891.
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