MMG 233 2014 Genetics & Genomics Wiki
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Introduction[1][2][3][]

A microRNA (abbreviated as miRNA) is a small non-coding RNA molecule of about 22 nucleotides in length, which functions to downregulate gene expression via repression of RNA translation, mRNA cleavage, deadenylation, and other methods.

  • MicroRNAs are too small to code for proteins.
  • MicroRNAs regulate most human genes.
  • The first miRNA was found in model organism C. elegans.

Biogenesis[4][5][]

MicroRNA-biogenesis-L
  1. miRNA gene is transcribed by RNA polymerase II (Pol II).
  2. Pri-miRNA is recognized by Drosha, a RNase III endonuclease, and both stem strands are cleaved off with a staggered cut at base of primary stem loop leaving 5’ phosphate and ~2 nucleotide (nt) 3’ overhang.
  3. Pre-miRNA is “exported” from Nucleus to Cytoplasm by Ran-GTP and Exportin5, an export receptor.
  4. Pre-miRNA is recognized by Dicer, another RNase III endonuclease, which trims off loop and terminal base pairs leaving 5’ phosphate and ~2 nt 3’ overhang.
  5. miRNA:miRNA* duplex is unwound by a helicase-like enzyme. The miRNA* (strand with more tightly paired 5’ end) is discarded and degraded.
  6. The miRNA strand is loaded into RISC (RNA-induced silencing complex) and targets complementary mRNAs.

               i. If miRNA is sufficiently complementary to mRNA, cleavage occurs via the RISC protein argonaute.

               ii. If miRNA is not sufficiently complementary, productive translation of mRNA is repressed.              

References[]

  1. David Bartel (Whitehead Institute/MIT/HHMI) Part 1: MicroRNAs: Introduction to MicroRNAs. (2014). Retrieved from http://www.youtube.com/watch?v=dupzE66J8u4&feature=youtube_gdata_player
  2. Ambros, V. (2004). The functions of animal microRNAs. Nature,431(7006), 350–355. doi:10.1038/nature02871
  3. microRNA. (2014, September 3). In Wikipedia, the free encyclopedia. Retrieved from http://en.wikipedia.org/w/index.php?title=MicroRNA&oldid=623976609
  4. Bartel, D. P. (2004). MicroRNAs: Genomics, Biogenesis, Mechanism, and Function.Cell116(2), 281–297. doi:10.1016/S0092-8674(04)00045-5
  5. RNA-induced silencing complex. (2014, August 24). In Wikipedia, the free encyclopedia. Retrieved from http://en.wikipedia.org/w/index.php?title=RNA-induced_silencing_complex&oldid=603881509
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