The Let-7 microRNA precursor was identified from a study of developmental timing in C. elegans, and was later shown to be part of a much larger class of non-coding RNAs termed microRNAs. miR-98 microRNA precursor from human is a let-7 family member. Let-7 miRNAs have now been predicted or experimentally confirmed in a wide range of species (MIPF0000002). miRNAs are initially transcribed in long transcripts (up to several hundred nucleotides) called primary miRNAs (pri-miRNAs), which are processed in the nucleus by Drosha and Pasha to hairpin structures of about 70 nucleotide. These precursors (pre-miRNAs) are exported to the cytoplasm by exportin5, where they are subsequently processed by the enzyme Dicer to a ~22 nucleotide mature miRNA. The involvement of Dicer in miRNA processing demonstrates a relationship with the phenomenon of RNA interference. Genomic Locations In human genome, the cluster let-7a-1/let-7f-1/let-7d is inside the region B at 9q22.3, with the defining marker D9S280-D9S1809. One minimal LOH (loss of heterozygosity) region, between loci D11S1345-D11S1316, contains the cluster miR-125b1/let-7a-2/miR-100. The cluster miR-99a/let-7c/miR-125b-2 is in a 21p11.1 region of HD (homozygous deletions). The cluster let-7g/miR-135-1 is in region 3 at 3p21.1-p21.2. The let-7 family The lethal-7 (let-7) gene was first discovered in the nematode as a key developmental regulator and became one of the first two known microRNAs (the other one is lin-4). Soon, let-7 was found in fruit fly, and identified as the first known human miRNA by a BLAST (basic local alignment search tool) research. The mature form of let-7 family members is highly conserved across species. In C.elegans In C.elegans, the let-7 family consists of genes encoding nine miRNAs sharing the same seed sequence. Among them, let-7, mir-84, mir-48 and mir-241 are involved in C.elegans heterochronic pathway, sequentially controlling developmental timing of larva transitions. Most animals with loss-of-function let-7 mutation burst through their vulvas and die, and therefore the mutant is lethal (let). The mutants of other let-7 family members have a radio-resistant phenotype in vulval cells, which may be related to their ability to repress RAS. In Drosophila There is only one single let-7 gene in the Drosophila genome, which has the identical mature sequence to the one in C.elegans. The role of let-7 has been demonstrated in regulating the timing of neuromuscular junction formation in the abdomen and cell-cycle in the wing. Furthermore, the expression of pri-, pre- and mature let-7 have the same rhythmic pattern with the hormone