PUBLICATION

Screening by deep sequencing reveals mediators of microRNA tailing in C. elegans

Authors
Vieux, K.F., Prothro, K.P., Kelley, L.H., Palmer, C., Maine, E.M., Veksler-Lublinsky, I., McJunkin, K.
ID
ZDB-PUB-211222-1
Date
2021
Source
Nucleic acids research   49: 11167-11180 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Adenosine Monophosphate/metabolism
  • Humans
  • RNA, Helminth/classification
  • RNA, Helminth/genetics*
  • RNA, Helminth/metabolism
  • Zebrafish/classification
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Caenorhabditis elegans Proteins/genetics*
  • Caenorhabditis elegans Proteins/metabolism
  • Cell Cycle Proteins/genetics*
  • Cell Cycle Proteins/metabolism
  • MicroRNAs/antagonists & inhibitors
  • MicroRNAs/classification
  • MicroRNAs/genetics*
  • MicroRNAs/metabolism
  • Conserved Sequence
  • Phylogeny
  • Mice
  • Gene Expression Regulation
  • Species Specificity
  • Half-Life
  • Chickens/classification
  • Chickens/genetics
  • Chickens/metabolism
  • Animals
  • RNA Stability
  • Caenorhabditis elegans/classification
  • Caenorhabditis elegans/genetics*
  • Caenorhabditis elegans/metabolism
  • RNA Interference
  • Uridine Monophosphate/metabolism*
  • Genome, Helminth*
PubMed
34586415 Full text @ Nucleic Acids Res.
Abstract
microRNAs are frequently modified by addition of untemplated nucleotides to the 3' end, but the role of this tailing is often unclear. Here we characterize the prevalence and functional consequences of microRNA tailing in vivo, using Caenorhabditis elegans. MicroRNA tailing in C. elegans consists mostly of mono-uridylation of mature microRNA species, with rarer mono-adenylation which is likely added to microRNA precursors. Through a targeted RNAi screen, we discover that the TUT4/TUT7 gene family member CID-1/CDE-1/PUP-1 is required for uridylation, whereas the GLD2 gene family member F31C3.2-here named GLD-2-related 2 (GLDR-2)-is required for adenylation. Thus, the TUT4/TUT7 and GLD2 gene families have broadly conserved roles in miRNA modification. We specifically examine the role of tailing in microRNA turnover. We determine half-lives of microRNAs after acute inactivation of microRNA biogenesis, revealing that half-lives are generally long (median = 20.7 h), as observed in other systems. Although we observe that the proportion of tailed species increases over time after biogenesis, disrupting tailing does not alter microRNA decay. Thus, tailing is not a global regulator of decay in C. elegans. Nonetheless, by identifying the responsible enzymes, this study lays the groundwork to explore whether tailing plays more specialized context- or miRNA-specific regulatory roles.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping