WormMine

WS294

Intermine data mining platform for C. elegans and related nematodes

Gene :

WormBase Gene ID  ? WBGene00002285 Gene Name  let-7
Sequence Name  ? C05G5.6 Brief Description  let-7 encodes a 21-nucleotide microRNA (also known as a small temporal RNA, or stRNA) that is conserved in bilateral animal species (including vertebrates, ascidians, hemichordates, molluscs, annelids and arthropods), but is not found in cnidarians, poriferans, fungi, plants, protists, archaea, or bacteria; let-7 is required for the transition from late larval to adult cell fates, and for larval viability; like lin-4, let-7 is complementary to sequences in the 3' untranslated regions of target genes that it negatively regulates; let-7 RNA expression is first detected at late larval stages and is negatively regulated by the product of one of its targets, hbl-1, in a negative feedback loop; the temporal regulatory element (TRE), situated about 1200 base pairs upstream of the start of the mature let-7 RNA, is both necessary and sufficient for temporal upregulation of let-7 transcription; DCR-1, ALG-1, and ALG-2 are required for the maturation and activity of let-7 stRNA; since let-7 homologs are expressed in zebrafish embryos and in adult annelids and molluscs, let-7 may have a conserved function in heterochronic developmental regulation in bilateria.
Organism  Caenorhabditis elegans Automated Description  Enables mRNA 3'-UTR binding activity. Involved in several processes, including negative regulation of Ras protein signal transduction; negative regulation of gene expression; and regulation of development, heterochronic. Part of RISC complex. Expressed in several structures, including gonad; hypodermis; somatic nervous system; touch receptor neurons; and vulval precursor cell. Used to study cancer.
Biotype  SO:0001265 Genetic Position  X :21.2192 ±0.067046
Length (nt)  ? 1732
Quick Links:
 

1 Organism

Name Taxon Id
Caenorhabditis elegans 6239

1 Synonyms

Value
WBGene00002285

Genomics

5 Transcripts

Class WormMine ID Sequence Name Length (nt) Chromosome Location
MiRNAPrimaryTranscript Transcript:C05G5.6.2 C05G5.6.2 891   X: 14743590-14744480
MiRNAPrimaryTranscript Transcript:C05G5.6.3 C05G5.6.3 707   X: 14743590-14744296
MiRNAPrimaryTranscript Transcript:C05G5.6.1 C05G5.6.1 1732   X: 14743590-14745321
MiRNA Transcript:C05G5.6b C05G5.6b 22   X: 14744191-14744212
MiRNA Transcript:C05G5.6a C05G5.6a 22   X: 14744234-14744255
 

Other

0 CDSs

0 RNAi Result

52 Allele

Public Name
gk964260
gk964029
gk962707
gk964028
gk963810
gk963581
WBVar01928581
q782
tm11366
gk301756
gk501874
gk301755
WBVar01760444
ma422ma423
h11385
WBVar00085527
WBVar00085529
WBVar00085528
WBVar00085531
WBVar01679712
WBVar00085530
WBVar00085532
zen162
zen165
zen168
WBVar01942208
zen171
WBVar01942207
ma393
ma388

1 Chromosome

WormBase ID Organism Length (nt)
X Caenorhabditis elegans 17718942  

1 Chromosome Location


Feature . Primary Identifier
Start End Strand
WBGene00002285 14743590 14745321 -1

3 Data Sets

Name URL
WormBaseAcedbConverter  
GO Annotation data set  
C. elegans genomic annotations (GFF3 Gene)  

1 Downstream Intergenic Region

WormBase ID Name Sequence Name Length (nt) Chromosome Location Organism
intergenic_region_chrX_14740120..14743589   3470 X: 14740120-14743589 Caenorhabditis elegans

43 Expression Clusters

Regulated By Treatment Description Algorithm Primary Identifier
  Neuronally enriched transcripts according to a comparison of neuronal nuclei IP samples to total nuclei using isolation of nuclei from tagged specific cell types (INTACT) technology. DESEQ2, fold change > 2 and FDR < 0.01. WBPaper00062103:neuron_enriched
  Transcripts that showed significantly decreased expression in atfs-1(cmh15) (null allele) animals comparing to in N2 animals at L4 larva stage. edgeR, fold change > 2, FDR < 0.05 WBPaper00060909:atfs-1(cmh15)_downregulated
  Transcripts that showed differential expression between 24 and 26 hours post hatching L2d and dauer committed larvae of daf-9(dh6), triggered by the dafachronic acid (DA) growth hormone. Cluster 3 genes increased expression transiently at 26 hour post hatching. Benjamini Hochberg corrected q-value < 0.01. WBPaper00053388:dauer_regulated_Cluster3
  Transcripts that showed significantly increased expression in mbl-1(syb4345), referred to as mbl-1long(ex7+), comparing to in N2 at L4 larva stage. DESeq2, Fold change > 2 and FDR < 0.05 WBPaper00066410:mbl-1(syb4345)_upregulated
  Transcripts that showed altered expression from P0 to F2 generation animals after N2 parental generation were treated with antimycin, but not in damt-1(gk961032) P0 to F2 animals after the parenal generaton were treated with antimycin. N.A. WBPaper00055862:antimycin_damt-1(gk961032)_regulated
  Transcripts that showed significantly increased expression in ints-1(RNAi) animals comparing to control RNAi animals, at late L3 larva stage. DESeq2, v1.12.0, fold change > 2, FDR < 0.05 WBPaper00057068:ints-4(RNAi)_upregulated
Bacteria infection: Pseudomonas aeruginosa PA14. 24 hours of exposure. Small RNAs (21-26nt) that showed significantly increased expression after L4 animals were exposed to P .aeruginosa strain PA14 for 24 hours. DESeq2, FDR < 0.05 WBPaper00056868:P.aeruginosa_upregulated_smallRNA
Bacteria diet: Sphingomonas aquatilis Yellow. Fed for 30 generations. Transcripts that showed significantly increased expression after fed by bacteria Sphingomonas aquatilis (Yellow) for 30 generations comparing to animals fed by E. coli OP50. DESeq2 fold change > 2, p-value < 0.01. WBPaper00061007:S.aquatilis_upregulated
  Transcripts that showed significantly increased expression in jmjd-5(zr1234) comparing to in N2 animals. DESeq2, adjusted p value < 0.01 and absolute log2FC > = 1. WBPaper00062156:jmjd-5(zr1234)_upregulated
  Transcripts that showed significantly decreased expression in numr-1/2(RNAi) animals comparing to control RNAi animals, at late L3 larva stage. DESeq2, v1.12.0, fold change > 2, FDR < 0.05 WBPaper00057068:numr-1(RNAi)_downregulated
  Transcripts that showed significantly increased expression in hsp-6(mg585) comparing to in N2 at L4 larva stage. EdgeR, fold change > 2, FDR < 0.001. WBPaper00056290:hsp-6(mg585)_upregulated
  Transcripts that showed significantly decreased expression in BAT525 [hmg-3 (tm2539) / dpy-5(e61) unc-13(e1091) I.] comparing to in N2 at 1-day post L4 adult hermaphrodite stage DESeq 2, fold change > 4, adjusted p-value < 0.05. WBPaper00055013:hmg-3(bar24)_downregulated
  Potental DAF-12 target genes identified by ChIP-chip analysis performed on strain ALF4 [daf-12 Affymetrix TAS software that computed for each probe estimates of fold enrichment (in linear scale) over hybridization with input DNA. At the same time, TAS calculated for each probe a p-value by applying a Wilcoxon signed rank test. A threshold of 2.5 was selected, which corresponds to probe intensities approximately 2.5 times stronger on the ChIP array than on the Input array. Additional TAS threshold parameters were MinRun=180 bp, MaxGap=300 bp. TAS analysis showed that the selected threshold of 2.5 corresponds approximately to a p-value of 0.01. WBPaper00040221:DAF-12_target_ALF4
  Transcripts that showed significantly decreased expression in nfki-1(cer1) animals at L4 larva stage, comparing to in N2 animals. Differentially expressed genes between wild type and knockouts were explored using DESeq2 R package (v.1.20.0) considering a threshold of adjusted p value < 0.01. WBPaper00060445:nfki-1(cer1)_downregulated_L4
  Transcripts that showed significantly increased expression in mdt-15(mg584gf) comparing to in N2 at L4 larva stage. EdgeR, fold change > 2, FDR < 0.001. WBPaper00056290:mdt-15(mg584)_upregulated
  Genes that showed significantly increased expression after exposure to 1mg/L MWCNTs from L1 larva to young adult. Transcripts with false discovery rate-corrected p-values < 0.05 and fold change > 2 were defined as differentially expressed. WBPaper00049377:MWCNT_upregulated
  Transcripts that were enriched in muscle in young adult animals, according to trans-splicing-based RNA tagging (SRT) and RNAseq. DESeq and Benjamini-Hochberg adjusted p-values were used. WBPaper00050053:muscle_enriched_Day4
  Transcripts that showed significantly increased expression in animals exposed to 2.5mM ketamine since L1 larva stage. DESeq2 (1.20.0), fold change > 2, p-value < 0.05. WBPaper00064788:ketamine_upregulated
  Transcripts that showed significantly increased expression in spt-16(RNAi) comparing to in vector control worm at L4 larva stage. DESeq 2, fold change > 4, adjusted p-value < 0.05. WBPaper00055013:spt-16(RNAi)_downregulated
  Transcripts that showed significantly decreased expression in ikb-1(nr2027) animals at L4 larva stage, comparing to in N2 animals. Differentially expressed genes between wild type and knockouts were explored using DESeq2 R package (v.1.20.0) considering a threshold of adjusted p value < 0.01. WBPaper00060445:ikb-1(nr2027)_downregulated_L4
  Transcripts that showed significantly decreased expression in set-26(tm2467) animals comparing to in N2. edgeR, 5% FDR. WBPaper00054410:set-26(tm2467)_downregulated
  Micro RNAs that showed significantly decreased expression in day 8 adults comparing to in day 1 adults in intestine. Differentially expressed miRNAs were identified using DEGseq based on unique molecular identifier (UMI). A minimum UMI sum of 10 in 3 replicates was set as the threshold of expression. MiRNAs with more than five reads were defined as expressed. Differential expression of miRNAs was analysed by t-test (P value < 0.05 and fold-change > 1.5 or < 0.67) after Box-Cox transformation. MiRNA targets were identified by TargetScanWorm (Release 6.2) and Pearson Correlation Coefficient smaller than -0.2. WBPaper00066447:Day8_vs_Day1_downregulated_intestine
  Transcripts that were enriched in muscle in day 12 animals, according to trans-splicing-based RNA tagging (SRT) and RNAseq. DESeq and Benjamini-Hochberg adjusted p-values were used. WBPaper00050053:muscle_enriched_Day12
  Transcripts that showed significantly decreased expression in set-9(rw5) animals comparing to in N2. edgeR, 5% FDR. WBPaper00054410:set-9(rw5)_downregulated
  Micro RNAs that showed significantly decreased expression in day 8 adults comparing to in day 1 adults in hypodermis. Differentially expressed miRNAs were identified using DEGseq based on unique molecular identifier (UMI). A minimum UMI sum of 10 in 3 replicates was set as the threshold of expression. MiRNAs with more than five reads were defined as expressed. Differential expression of miRNAs was analysed by t-test (P value < 0.05 and fold-change > 1.5 or < 0.67) after Box-Cox transformation. MiRNA targets were identified by TargetScanWorm (Release 6.2) and Pearson Correlation Coefficient smaller than -0.2. WBPaper00066447:Day8_vs_Day1_downregulated_hypodermis
  miRNAs that showed significantly increased expression in pry-1(mu38) comparing to in N2. Fold change > 2, FDR < 0.05 WBPaper00057033:pry-1(mu38)_upregulated
  MicroRNAs that showed significantly decreased expression in alg-5(ram2), comparing to in N2. DESeq2, Fold change > 1.5. WBPaper00051404:alg-5(ram2)_downregulated_miRNA
  micro RNAs that exhibit changes in expression during adulthood (p-value < = 0.05). Authors searched for targets with seed matches of perfect Watson-Crick base-pair complementarity to positions two-eight of the miRNAs (counting from the 5' end). In order to consider these seed matches as potential target sites, authors required a minimal cut-off for binding specificity of the remainder of the miRNA to the target. Recent evidence suggests that this is not required for function in humans, but 3' binding does occur in studies of C. elegans. Authors used the scoring algorithm from Robins et al. (2005). The binding cut-off is determined by creating a second-order Markov model of the background for the 3' UTRs. The cut off was p-value < = 0.05. WBPaper00028344:adult_expr_change
  Micro RNAs that showed significantly decreased expression in hrpk-1(tm5522) comparing to in N2 at L4 larva stage. DESeq, fold change > 2, p-value <= 0.05. WBPaper00058673:hrpk-1(tm5522)_downregulated_miRNA_L4
  MicroRNAs that showed significantly increased expression in alg-2(ok304), comparing to in N2. DESeq2, Fold change > 1.5. WBPaper00051404:alg-2(ok304)_upregulated_miRNA

20 Expression Patterns

Remark Reporter Gene Primary Identifier Pattern Subcellular Localization
    Expr12867 GFP expression appeared in the seam cells at the very beginning of the L4 stage and continued on through adulthood. GFP was never seen in the seam cells before the L3-to-L4 transition in a wild-type background (100%, n 80 animals). Seam cell expression of let-7::gfp is significant as let-7 is normally required for seam cell development. Nontemporally regulated GFP expression was observed in other parts of the worm, including the pharynx, intestinal cells, muscle cells, and neurons.  
    Expr15759    
    Expr12021 During the L1 and L2 stages, Plet-7::gfppest expression is detected primarily in the intestine, the pharynx, and some neurons. Beginning in the L3, Plet-7::gfppest expression is detected in seam and vulva precursor cells, as well as the body wall muscle, in addition to the tissues observed in L1/L2 stage animals. Plet-7::gfppest is expressed strongly in the vulva and seam during the L4.  
    Expr8408 Expression detected from late embryos to adults. In late embryos to L1, expression is seen in dnc and intestine. From L2 to adults, expression is detected in almost all tissues except germline; specifically muscle, rectum, vulva, spermatheca, pharynx, intestine, vnc, dnc, nerve ring, hypodermis.  
    Expr10882 The let-7 promoter drives GFP expression in AVM and ALM touch neurons in L2-stage and YA animals. Expression of the mature let-7 micro-RNA is almost undetectable from embryonic to L2 stages and becomes apparent at L3. lin-41 is broadly expressed in the nervous system at the L2 stage. GFP expression is seen in the head ganglion, tail neurons, SDQR, AVM, ALM, and ventral cord motor neurons.  
Picture: Fig 2A.   Expr8397 Northern blot temporal expression: L3 to adult.  
plet-7A::GFP and plet-7B::GFP expression differs in intestine, hypodermal, and seam cells.   Expr10699 let-7 primary transcripts are first detected at the end of the first larval stage and exhibit pulses of expression near the molt of each larval stage. Both of the plet-7::GFP constructs drove temporally regulated expression, initially observed at the end of the first larval stage (L1). Starting in late L1 (~10 h at 25°C), robust GFP was seen in muscle and neuronal cells in the head, including the nerve ring. Midway through L2, GFP accumulated in the neurons and muscle cells of the tail, body wall muscle (BWM), and ventral nerve cord (VNC). Beginning in L3, all transgenic lines began to express GFP in vulva precursor cells. After the onset of GFP expression in a particular tissue, it was maintained until adults became gravid with embryos (~52 h at 25° C). GFP was not detected in the germ line. Although plet-7A::GFP and plet-7B::GFP transgenics showed similar spatio-temporal expression patterns in most cell types, they were not entirely overlapping. In hypodermal and seam cells, the plet-7B::GFP reporter produced a robust GFP signal at the L3 stage. However, plet-7A::GFP animals exhibited only weak, transient expression of GFP in the hypodermal cells beginning at the L3 stage. Early in the second stage of development, all intestinal cells showed high expression of GFP in plet-7B::GFP transgenic animals, while GFP was undetectable in the intestine of plet-7A::GFP transgenic animals.  
    Expr12248 let-7 promoter directed temporal gfp expression in the seam cells of transgenic animals at the early L4 stage and in the adult. let-7 was observed in the anchor cell at L3 and in the distal tip cells at the adult stage. lin-4 and let-7 were weakly expressed in the anchor cell, which is required for proper vulval patterning, and in the P5.p, P6.p, and P7.p cells that will later differentiate into the mature vulva.  
    Expr9613 Fluorescence was observed at the end of the L1 stage in transgenic worms that express GFP fused to the pri-let-7B start site. Detection of GFP mRNA, driven by both let-7 promoter A and B sequences in the transgenic worms, mirrored that of endogenous let-7 primary transcripts, indicating that expression of let-7 is repressed largely at the transcriptional level from embryogenesis until the late L1 stage. Consistent with the reporter analysis, pri-let-7 was first observed during the late L1 stage. We detected all three pri-let-7 isoforms, and coordinate expression of these isoforms oscillated throughout development. The low levels of pri-let-7 at most mid-larval time points and the slight shifts in the timing of pri-let-7 expression between experiments indicate that expression of endogenous pri-let-7 transcripts is dynamic, and that even slight changes in culture conditions can affect the rate of development and thus pri-let-7 expression. GFP mRNA levels of the let-7 promoter reporter oscillated with a frequency identical to that of endogenous pri-let-7 expression, suggesting that transcriptional mechanisms largely control the cycling pattern of pri-let-7 expression. Consistent with previous reports, pre- and mature let-7 RNAs were undetectable until the L3 stage. In the L3 and L4 stages, levels of pre-let-7 oscillated in parallel to those of pri-let-7, while mature let-7 accumulated to a relatively constant level.  
    Expr12251 For each of the mir::GFP-pest reporters (Plin-4::GFP-pest, Plet-7::GFP-pest, mir-1::GFP-pest) post-embryonic GFP-pest expression was first detected at approximately 14 hours post L1 arrest. Once transcriptionally activated, Plin-4::GFP-pest and Plet-7::GFP-pest reporters peak in expression by 18-20 hours and diminish with similar kinetics. For animals expressing the Plet-7::GFP-pest reporter GFP-pest expression was monitored for longer periods after release from L1 arrest. Consistent with the highly pulsatile nature of this expression pattern, GFP-pest expression was reinitiated at 30 hours, which correlates with the later portions of the L2 stage. While transcriptional activation of the Pmir-1::GFP-pest reporter was also initiated at 14 hours post-L1 arrest, the peak of Pmir-1::GFPpest expression occurred at a later time point, and diminished with slower kinetics, as compared to Plin-4::GFP-pest and Plet-7::GFP-pest expression.The majority of animals which harbor the Plin-4::GFP-pest transgene cease GFP-pest expression by L3 ecdysis and resume expression by the mid-L4 stage. The pulse of Plin-4::GFP-pest expression at the L4 stage extends through the early portion of young adulthood and completely overlaps with the lethargus period in all animals. Plet-7::GFP-pest expression followed a similar pattern. However, GFP-pest expression was more variable at the L3-to-L4 transition and L4-specific induction of this transgene was primarily restricted to the lethargus period. In contrast to the expression profiles of the lin-4 and let-7 reporters, induction of Pmir-1::GFP-pest expression began during, or immediately after, L3 ecdysis and persisted into the L4 stage. A second pulse of Pmir-1::GFP-pest expression completely overlapped with the L4 lethargus period and continued into early adulthood. Collectively, these results suggest that the expression patterns of lin-4, let-7 and mir-1 are dynamic throughout development and that the cyclical transcription of these miRNAs is mediated by their cognate promoter sequences.  
    Expr11388 Both pri-let-7 and SL1-pri-let-7 were dynamically expressed during the L4 stage, starting from low levels, peaking around the time of maximum lin-42 levels, and subsequently declining.  
    Expr2521 No signal detected in embryos, L1 and L2 larva. Intense signals detected in L3, L4 larva, adults, and glp-4(bn2) adults.  
Previous studies did not detect the four let-7 family members until the L3 stage, but earlier expression of all four microRNAs was detected by enhancing the sensitivity of detection.   Expr3774 When normalized to U6 expression, let-7 RNA reached half-maximal expression at about the L4 stage.  
    Expr12874 Unspliced let-7 primary transcripts are expressed in L3-larvae, L4-larvae and adults.  
    Expr2430 The expression and function of the let-7 RNA in C. elegans begins during the third larval stage, when the gene specifies a transition from late larval to adult cell fates, and continues at all subsequent stages.  
    Expr12875 Mature let-7 RNAs are detect din L4 larvae and adult worms.  
    Expr2658 Precursor miRNA: Very weak expression detected in L4. No expression detected in embryo, L1-L3 and adult. mature miRNA: Strong expression in L4 and adult. Weak expression in L3. No expression detected in embryo, L1 and L2.  
    Expr960 let-7 RNA was not detected at embryonic, L1 or L2 stages; low-level expression was detected at the early L3 stage; and high-level expression was detected at the early L4 and adult stages.  
    Expr1669 Expressed in L3, L4 and adults.  
Figure S4.   Expr12022 pri-let-7 miRNA transcript levels oscillate during wild-type larval development, peaking once per larval stage.  

15 GO Annotation

Annotation Extension Qualifier
  involved_in
  involved_in
  involved_in
  involved_in
has_input(WB:WBGene00003026) enables
  involved_in
  enables
  part_of
  part_of
  involved_in
  part_of
  involved_in
  involved_in
  involved_in
  involved_in

0 Homologues

1 Locations


Feature . Primary Identifier
Start End Strand
WBGene00002285 14743590 14745321 -1

15 Ontology Annotations

Annotation Extension Qualifier
  involved_in
  involved_in
  involved_in
  involved_in
has_input(WB:WBGene00003026) enables
  involved_in
  enables
  part_of
  part_of
  involved_in
  part_of
  involved_in
  involved_in
  involved_in
  involved_in

6 Regulates Expr Cluster

Regulated By Treatment Description Algorithm Primary Identifier
  Proteins that showed differential expression in (B) let-7(mg279);[let-7 sponge] when comparing to (A) [let-7 sponge], and in (C) gld-1(op236); let-7(mg279);[let-7 sponge] when comparing to (A) [let-7 sponge] N.A. WBPaper00044501:gld-1_let-7_regulated
  Proteins identified by MudPIT in let-7(wt) miRNA pulldown. Fold change > 4 enriched in miRNA pulldowns over the scrambled control, WBPaper00064080:let-7_miRNA_interacting
  Transcripts upregulated consistently in let-7(n2853), lin-41(xe11) and lin-41(xe11); let-7(n2853) mutant worms, compared to wild-type worms (on RPF, ribosome-protected fragments, level) N.A. WBPaper00050717:let-7(n2853)_lin-41(xe11)_upregulated
  Genes down-regulated more than 2-fold in let-7(n2853) compared to wild-type. Paired t-test. Expression level change of more than 2 fold is the cut-off. WBPaper00042165:let-7_downregulated
  Transcripts downregulated consistently in let-7(n2853), lin-41(xe11) and lin-41(xe11); let-7(n2853) mutant worms, compared to wild-type worms (on RPF, ribosome-protected fragments, level) N.A. WBPaper00050717:let-7(n2853)_lin-41(xe11)_downregulated
  Genes up-regulated more than 2-fold in let-7(n2853) compared to wild-type. Paired t-test. Expression level change of more than 2 fold is the cut-off. WBPaper00042165:let-7_upregulated

1 Sequence

Length
1732

1 Sequence Ontology Term