Transcription of the C. elegans let-7 microRNA is temporally regulated by one of its targets, hbl-1.
The let-7 family of microRNAs (miRNAs) are important regulators of developmental timing and cell differentiation and are often misexpressed in human cancer. In C. elegans, let-7 controls cell fate transitions from larval stage 4 (L4) to adulthood by post-transcriptionally down-regulating lineage-abnormal 41 (lin-41) and hunchback-like 1 (hbl-1). Primary let-7 (pri-let-7) transcripts are up-regulated in the L3, yet little is known about what controls this transcriptional up-regulation. We sought factors that either turn on let-7 transcription or keep it repressed until the correct time. Here we report that one of let-7's targets, the transcription factor Hunchback-like 1 (HBL-1), is responsible for inhibiting the transcription of let-7 in specific tissues until the L3. hbl-1 is a known developmental timing regulator and inhibits adult development in larval stages. Therefore, one important function of HBL-1 in maintaining larval stage fates is inhibition of let-7. Indeed, our results reveal let-7 as the first known target of the HBL-1 transcription factor in C. elegans and suggest a negative feedback loop mechanism for let-7 and HBL-1 regulation.
Roush
Sarah F
SF
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Slack
Frank J
FJ
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007814:Larva; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; D014157:Transcription Factors; C474486:hbl-1 protein, C elegans; C452194:lin-4 microRNA, C elegans