A secondary structure and sequence conservation diagram for Bantam microRNA.
A microRNA (abbreviated miRNA) is a short ribonucleic acid (RNA) molecule found in eukaryotic cells. A microRNA molecule has very few nucleotides (an average of 22) compared with other RNAs.
miRNAs are post-transcriptional regulators that bind to complementary sequences on target messenger RNA transcripts (mRNAs), usually resulting in translational repression or target degradation and gene silencing.[1][2] The human genome may encode over 1000 miRNAs,[3][4] which may target about 60% of mammalian genes[5][6] and are abundant in many human cell types.[7]
miRNAs show very different characteristics between plants and metazoans. In plants the miRNA complementarity to its mRNA target is nearly perfect, with no or few mismatched bases. In metazoans, on the other hand, miRNA complementarity typically encompasses the 5′ bases 2-7 of the microRNA, the microRNA seed region,[5][8] and one miRNA can target many different sites on the same mRNA or on many different mRNAs. Another difference is the location of target sites on mRNAs. In metazoans, the miRNA target sites are in the three prime untranslated regions (3′UTR) of the mRNA. In plants, targets can be located in the 3′ UTR but are more often in the coding region itself.[9] MiRNAs are well conserved in eukaryotic organisms and are thought to be a vital and evolutionarily ancient component of genetic regulation.[10][11][12][13]
The first miRNAs were characterized in the early 1990s. However, miRNAs were not recognized as a distinct class of biological regulators with conserved functions until the early 2000s. Since then, miRNA research has revealed multiple roles in negative regulation (transcript degradation and sequestering, translational suppression) and possible involvement in positive regulation (transcriptional and translational activation). By affecting gene regulation, miRNAs are likely to be involved in most biological processes.[14][15][16][17][18][19][20] Different sets of expressed miRNAs are found in different cell types and tissues.[21]
Aberrant expression of miRNAs has been implicated in numerous disease states, and miRNA-based therapies are under investigation.[22][23][24]
MicroRNAs were discovered in 1993 by Victor Ambros, Rosalind Lee and Rhonda Feinbaum during a study of the gene lin-14 in C. elegans development.[25] They found that LIN-14 protein abundance was regulated by a short RNA product encoded by the lin-4 gene. A 61-nucleotide precursor from the lin-4 gene matured to a 22-nucleotide RNA that contained sequences partially complementary to multiple sequences in the 3’ UTR of the lin-14 mRNA. This complementarity was both necessary and sufficient to inhibit the translation of the lin-14 mRNA into the LIN-14 protein. Retrospectively, the lin-4 small RNA was the first microRNA to be identified, though at the time, it was thought to be a nematode idiosyncrasy. Only in 2000 was a second RNA characterized: let-7, which repressed lin-41, lin-14, lin-28, lin-42, and daf-12 expression during developmental stage transitions in C. elegans. let-7 was soon found to be conserved in many species,[26][27] indicating the existence of a wider phenomenon.
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