A miRNA or microRNA is a small non-coding RNA molecule (ca. 22 nucleotides) found in plants and animals which functions in transcriptional and post-transcriptional regulation of gene expression. miRNAs are encoded by eukaryotic nuclear DNA and function via base-pairing with complementary sequences within mRNA molecules, which commonly ends in gene silencing via translational repression or target degradation.
Discovery of miRNA
Victor Ambros, Rosalind Lee, and Rhonda Feinbaum discovered miRNAs in 1993 while studying the nematode Caenorhabditis elegant (C. elegans) regarding the gene lin-14. They found out that the lin-14 could be regulated by a short RNA product from lin-4, a gene that transcribed a 61 nucleotide precursor that matured to a 22 nucleotide mature RNA, which contained sequences partially complementary to multiple sequences in the 3’ UTR of the lin-14 mRNA — a complementarity that was sufficient and necessary to inhibit the translation of lin-14 mRNA.
Looking backwards, this was the first microRNA to be identified, though at the time Ambros, Lee, and Feinbaum wondered if it would be nematode idiosyncrasy.
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Only in 2000 was it discovered that let-7 repressed lin-41, lin-14, lin28, lin42 and daf12 mRNA during transition in developmental stages in C. elegant. It was also revealed that the let-7 function was phylogenetically conserved in species beyond nematodes. After this, it became evident that the short non-coding RNA identified in 1993 was part of a wider phenomenon.
Nowadays there are more than 4000 miRNAs identified in all studied eukaryotes, including mammals, fungi, and plants. So far in humans, over 700 miRNAs have been discovered, and it’s estimated that over 800 more exist.
The comparison of miRNAs between species can help to define molecular evolutionary history, considering that complexity of an organism’s phenotype may reflect the complexity of the microRNA present in the genotype.
Genetic codes and miRNA
The human genome project mapped its first chromosome in 1999. By then, it was predicted it would contain more than 100,000 protein coding genes. Yet, only around 20,000 protein coding genes were identified (International Human Genome Sequencing Consortium, 2004). After that, much of the non-protein-coding DNA was considered “useless,” even when the conventional knowledge defends that much, if not most of the genome, is functional.
Ever since, the advent of sophisticated bioinformatics approaches combined with genome tiling studies examining the transcriptome, systematic sequencing of full length cDNA libraries and experimental validation, have revealed that many transcripts are for non protein coding.
Thanks to their abundant occurrence and extensive potential, miRNAs play many roles in physiology, such as cell differentiation, proliferation, apoptosis to the endocrine system, haematopoiesis, fat metabolism, limb morphogenesis. miRNAs display different expression profiles from tissue to tissue, reflecting the diversity in cellular phenotypes and as such suggest a role in tissue differentiation and maintenance.
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