The Period protein homolog LIN-42 negatively regulates microRNA biogenesis in C. elegans.
MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate gene expression in many multicellular organisms. They are encoded in the genome and transcribed into primary (pri-) miRNAs before two processing steps that ultimately produce the mature miRNA. In order to generate the appropriate amount of a particular miRNA in the correct location at the correct time, proper regulation of miRNA biogenesis is essential. Here we identify the Period protein homolog LIN-42 as a new regulator of miRNA biogenesis in Caenorhabditis elegans. We mapped a spontaneous suppressor of the normally lethal let-7(n2853) allele to the lin-42 gene. Mutations in this allele (ap201) or a second lin-42 allele (n1089) caused increased mature let-7 miRNA levels at most time points when mature let-7 miRNA is normally expressed. Levels of pri-let-7 and a let-7 transcriptional reporter were also increased in lin-42(n1089) worms. These results indicate that LIN-42 normally represses pri-let-7 transcription and thus the accumulation of let-7 miRNA. This inhibition is not specific to let-7, as pri- and mature levels of lin-4 and miR-35 were also increased in lin-42 mutants. Furthermore, small RNA-seq analysis showed widespread increases in the levels of mature miRNAs in lin-42 mutants. Thus, we propose that the period protein homolog LIN-42 is a global regulator of miRNA biogenesis.
Division of Biology, University of California at San Diego, La Jolla, CA 92093-0349, USA; Department of Biology, Colgate University, Hamilton, NY 13323, USA. Electronic address: pvanwynsberghe@colgate.edu.
Priscilla M
PM
Van Wynsberghe
Division of Biology, University of California at San Diego, La Jolla, CA 92093-0349, USA.
Emily F
EF
Finnegan
Division of Biology, University of California at San Diego, La Jolla, CA 92093-0349, USA; Department of Cellular and Molecular Medicine, Institute for Genomic Medicine, Stem Cell Program, University of California at San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
Thomas
T
Stark
Department of Biology, Colgate University, Hamilton, NY 13323, USA.
Evan P
EP
Angelus
Department of Biology, Colgate University, Hamilton, NY 13323, USA.
Kathryn E
KE
Homan
Department of Cellular and Molecular Medicine, Institute for Genomic Medicine, Stem Cell Program, University of California at San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
Gene W
GW
Yeo
Division of Biology, University of California at San Diego, La Jolla, CA 92093-0349, USA. Electronic address: apasquinelli@ucsd.edu.
Amy E
AE
Pasquinelli
D000818:Animals; D015152:Blotting, Northern; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D003433:Crosses, Genetic; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009841:Oligonucleotides / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C400538:LIN-42 protein, C elegans; C570417:MIRN35 microRNA, C elegans; D035683:MicroRNAs; D009841:Oligonucleotides; D014157:Transcription Factors; C474488:let-7 microRNA, C elegans; C452194:lin-4 microRNA, C elegans
C. elegans; Let-7; Lin-42; MicroRNA; Period