A genetic interactome of the let-7 microRNA in C. elegans.
The heterochronic pathway controls temporal patterning during Caenorhabditis elegans larval development. The highly conserved let-7 microRNA (miRNA) plays a key role in this pathway, directing the larval-to-adult (L/A) transition. Hence, knowledge of the genetic interactome of let-7 has the potential to provide insight into both control of temporal cell fates and mechanisms of regulation and function of miRNAs. Here, we report the results of a genome-wide, RNAi-based screen for suppressors of let-7 mutant vulval bursting. The 201 genetic interaction partners of let-7 thus identified include genes that promote target silencing activity of let-7, seam cell differentiation, or both. We illustrate the suitability of our approach by uncovering the mitotic cyclin-dependent kinase CDK-1 as a downstream effector of let-7 that affects both seam cell proliferation and differentiation, and by identifying a core set of candidate modulators of let-7 activity, which includes all subunits of the condensin II complex. We propose that the genes identified in our screen thus constitute a valuable resource for studies of the heterochronic pathway and miRNAs.
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland.
Magdalene
M
Rausch
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland.
Matyas
M
Ecsedi
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland.
Hrishikesh
H
Bartake
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Almuth
A
Müllner
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. Electronic address: helge.grosshans@fmi.ch.
Helge
H
Grosshans
D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D016203:CDC2 Protein Kinase / Q000096:biosynthesis / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000235:genetics*; D046912:Multiprotein Complexes / Q000235:genetics; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C095571:LIN-29 protein, C elegans; D035683:MicroRNAs; D046912:Multiprotein Complexes; D014157:Transcription Factors; C108312:condensin complexes; C474488:let-7 microRNA, C elegans; D016203:CDC2 Protein Kinase; D000251:Adenosine Triphosphatases
C. elegans; CDC-25.2; CDK-1; Cell cycle; Condensin; Condensin II complex; Developmental timing; Differentiation; Heterochronic; Hypodermis; LIN-29; NCC-1; Vulva; col-19; let-7; miRNA regulation; miRNA target; microRNA