The Period protein homolog LIN-42 negatively regulates microRNA biogenesis in C. elegans

Dev Biol. 2014 Jun 15;390(2):126-35. doi: 10.1016/j.ydbio.2014.03.017. Epub 2014 Mar 31.


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.

Keywords: C. elegans; Let-7; Lin-42; MicroRNA; Period.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Crosses, Genetic
  • Gene Expression Regulation, Developmental / genetics*
  • MicroRNAs / biosynthesis*
  • MicroRNAs / metabolism
  • Mutation / genetics
  • Oligonucleotides / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Caenorhabditis elegans Proteins
  • LIN-42 protein, C elegans
  • MIRN35 microRNA, C elegans
  • MicroRNAs
  • Oligonucleotides
  • Transcription Factors
  • let-7 microRNA, C elegans
  • lin-4 microRNA, C elegans