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Example sentences for: let-
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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.
Another notable cluster that includes previously identified miRNAs is one containing mir-100 , let-7 and mir-125 (Figure 7c).
This contrasts with observations of miRNAs in vertebrates, where the majority of known miRNAs are members of paralogous gene sets [ 31 ] . The most extreme examples of this disparity are let-7 and mir-29 , which are present in single copies in Drosophila , but are represented by thirteen and six distinct human homologs, respectively.
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 ] .
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