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Example sentences for: let-
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Although complementary sites for both miRNAs are found in the 3' UTRs of several putative nematode targets, these miRNAs are not physically linked in the C. elegans genome and their mutant phenotypes are principally due to misregulation of different transcripts [ 4 5 6 8 ] . The function of these miRNAs has not yet been explicitly demonstrated in other species, but Drosophila let-7 is regulated at the larval-pupal transition by ecdysone [ 49 ] , and all three members of this cluster are present in other insects and in vertebrates, thus implying broadly conserved functions.
Our collective ignorance of the totality of non-coding RNA genes was laid bare by recent work on microRNAs (miRNAs), an abundant family of 21-22 nucleotide non-coding RNAs [ 2 3 ] . The founding members of this family, lin-4 and let-7, were identified through forward analysis of extant Caenorhabditis elegans mutants [ 4 5 ] . Both of these RNAs are post-transcriptional regulators of developmental timing that function by binding to the 3' untranslated regions (3' UTRs) of target genes [ 5 6 7 8 ] . Although they were long regarded as genetic curiosities possibly specific to nematodes, let-7 was subsequently found to be broadly conserved across bilaterian evolution [ 9 ] and miRNA genes are now recognized as a pervasive and widespread feature of animal and plant genomes [ 10 11 12 13 14 15 16 ] .
This could explain why individual let-7 or miR-125 mutants with strong developmental defects have not yet been identified in Drosophila by genetic means.
For example, 41% of miRNAs cloned from HeLa cells are variants of let-7, 28% of human brain miRNAs are variants of miR-124, and 45% of miRNAs cloned from human heart and 32% of those cloned from early Drosophila embryos are miR-1 [ 10 29 ] . In fact, it has been opined that few additional mammalian miRNAs will be easily identified by the direct cloning method [ 30 ] .
The starting point for our studies was a reference set of 24 Drosophila pre-miRNA sequences ( let-7 , the 21 originally identified by Lagos-Quintana and colleagues, mir-125 , and a previously undescribed paralog of mir-2 that we named mir-2c [ 9 10 29 ] ). We analyzed this set to derive rules and determine parameters that specifically describe known miRNA genes within anonymous genomic sequence.
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