Most Caenorhabditis elegans microRNAs are individually not essential for development or viability

Abstract

MicroRNAs (miRNAs), a large class of short noncoding RNAs found in many plants and animals, often act to posttranscriptionally inhibit gene expression. We report the generation of deletion mutations in 87 miRNA genes in Caenorhabditis elegans, expanding the number of mutated miRNA genes to 95, or 83% of known C. elegans miRNAs. We find that the majority of miRNAs are not essential for the viability or development of C. elegans, and mutations in most miRNA genes do not result in grossly abnormal phenotypes. These observations are consistent with the hypothesis that there is significant functional redundancy among miRNAs or among gene pathways regulated by miRNAs. This study represents the first comprehensive genetic analysis of miRNA function in any organism and provides a unique, permanent resource for the systematic study of miRNAs.

Invited review: decoding the microRNA response to hypoxia

“…Such rapidity and efficiency may be crucial to counteract variable fluctuations in the environmental milieu such as oxygen levels. The fact that few functions have been assigned for miRNA mutants that are cultured in standard laboratory conditions suggests that they have discrete functions and perhaps act as responders to fluctuations in environmental stress [45,54]. Therefore, miRNA profiling after environmental stress and exposure of mutant animals and cells to environmental challenges may reveal novel mechanistic roles.…”

“…In fact, a survey of miRNA genetic mutants in C. elegans found that the majority of miRNAs are dispensable in normal laboratory conditions [54]. This work suggests that miRNAs have (1) discrete cellular functions, such as for lsy-6 which regulates left/right patterning of the ASE pair of neurons in the C. elegans chemosensory system [35] or (2) act as buffers to provide robustness to genetic networks when subjected to genetic or environment perturbation, such as miR-7 during sensory organ development in Drosophila [51].…”

Can the ‘neuron theory’ be complemented by a universal mechanism for generic neuronal differentiation

“…Somewhat surprisingly, however, mutational inactivation in C. elegans (Miska et al 2007) and D. melanogaster (Weng and Cohen 2012;Sun et al 2012), which in contrast to mammals possess only one gene coding for miR-124, leaves homozygous mutants viable and without gross abnormalities. In Drosophila, a range of mutant phenotypes can be found, notably compromised of neuronal progenitor proliferation with a decreased number of Elav-positive cells per type I neuroblast-derived clone (Weng and Cohen 2012), and incomplete transition from neuroblast to neuronal gene expression signature (Sun et al 2012), but no complete failure of neuron generation.…”

Feminized tassels of maize mop1 and ts1 mutants exhibit altered levels of miR156 and specific SBP-box genes

“…Reciprocally, reduction of the microRNA alone may not be suYcient to cause upregulation of the target without the necessary activators or transcription factors. Taken together, these studies suggest that regulatory redundancies, either between microRNAs or among microRNAs and other regulatory factors, tend to maintain expression levels of key targets to ensure normal development (Moss 2007;Miska et al 2007). There are both sequence and genomic structural similarities among the speciWc maize SBP-box genes whose mRNA levels are altered in feminized tassels.…”

“…A wealth of data in C. elegans supports this hypothesis. Systematic knockouts of numerous individual microRNA genes demonstrate that the majority are not critical for viability or normal development (Miska et al 2007), and that double or triple knockouts are sometimes required to disrupt normal developmental pathways (Abbott et al 2005). Furthermore, accumulation of the microRNA alone appears to be insuYcient to cause a downregulation of the target in all cases (Moss 2007) suggesting that other mechanisms and factors are needed.…”