In genetics, a miRNA (micro-RNA) is a form of single-stranded RNA which is typically 20-25 nucleotides long, and is thought to regulate the expression of other genes. miRNAs are RNA genes which are transcribed from DNA, but are not translated into protein. The DNA sequence that codes for an miRNA gene is longer than the miRNA. This DNA sequence includes the miRNA sequence and an approximate reverse complement. When this DNA sequence is transcribed into a single-stranded RNA molecule, the miRNA sequence and its reverse-complement base pair to form a double stranded RNA hairpin loop; this forms a primary miRNA structure (pri-miRNA). Drosha, a nuclear enzyme, cleaves the base of the hairpin to form pre-miRNA. The pre-miRNA molecule is then actively transported into the nucleus by Exportin 5, a carrier protein. The Dicer enzyme then cuts 20-25 nucleotides from the base of the hairpin to release the mature miRNA.

The function of miRNAs appears to be in gene regulation. For that purpose, a miRNA is complementary to a part of one or more messenger RNAs (mRNAs), usually at a site in the 3' UTR. The annealing of the miRNA to the mRNA inhibits protein translation. In some cases, the formation of the double-stranded RNA through the binding of the miRNA triggers the degradation of the mRNA transcript through a process similar to RNA interference (RNAi), though in other cases it is believed that the miRNA complex blocks the protein translation machinery or otherwise prevents protein translation without causing the mRNA to be degraded.

This effect was first described for the worm Caenorhabditis elegans in 1993 by R. C. Lee of Harvard University. As of 2002, miRNAs have been confirmed in various plants and animals, including C. elegans, human and the plant Arabidopsis thaliana. Genes have been found in bacteria that are similar in the sense that they control mRNA abundance or translation by binding an mRNA by base pairing, however they are not generally considered to be miRNAs because the Dicer enzyme is not involved.

The term miRNA was first introduced in a set of three articles in Science (26 October 2001) [1]

In plants, similar RNA species termed short-interfering RNAs siRNAs are used to prevent the transcription of viral RNA. While this siRNA is double-stranded, the mechanism seems to be closely related to that of miRNA, especially taking the hairpin structures into account. siRNAs are also used to regulate cellular genes, as miRNAs do.

The activity of an miRNA can be experimentally blocked using a Morpholino antisense oligo.

References

• This paper defines miRNA and proposes guidelines to follow in classifying RNA genes as miRNA. Victor Ambros, Bonnie Bartel, David P. Bartel, Christopher B. Burge, James C. Carrington, Xuemei Chenand, Gideon Dreyfuss, Sean R. Eddy, Sam Griffiths-Jones, Mhairi Marshall, Marjori Matzke, Gary Ruvkun and Thomas Tuschl (2003) "A uniform system for microRNA annotation", RNA, 9: 277-279. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12592000&dopt=Abstract
• This paper discusses the processes that miRNA and siRNAs are involved in, in the context of 2 articles in the same issue of the journal Science. David Baulcombe (2002) "An RNA Microcosm", Science, 297: 2002-2003. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12242426&dopt=Abstract
• This paper describes the discovery of lin-4, the first miRNA to be discovered (editor's note: in fact, no Wikipedia editor has yet read this paper, only made inferences from a citation). Lee, R.C., Feinbaum, R.L. and Ambros, V. (1993) "The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14", Cell, 75: 843–854. This paper, as well as other papers from the Ambros lab on miRNAs , is available on this page http://banjo.dartmouth.edu/lab/VRA_pubs.htm

External links

• The miRNA Registry