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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.
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.
Our observation that the temporal expression profile of miR-100 (Figure 5d) is similar to that described for let-7 and miR-125 (that is, expression is initiated during larval/pupal development and continues through adulthood [ 9 29 ] ) is consistent with probable coordinate expression of all three as a single pri-miRNA transcript, and may further implicate miR-100 in developmental timing.
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 ] .
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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