Dual Regulation of the lin-14 Target mRNA by the lin-4 miRNA

Hayes, Gabriel D.; Ruvkun, Gary

doi:10.1371/journal.pone.0075475

Cited by 10 publications

(11 citation statements)

References 26 publications

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“…remanei it is composed by 17 members, while C . brenneri has 27 [ 92 ]. Most embryo cells express mir-35 members, first at the onset of gastrulation, with a peak at the onset of elongation [ 11 , 57 , 60 ].…”

Section: Resultsmentioning

confidence: 99%

High-Throughput Profiling of Caenorhabditis elegans Starvation-Responsive microRNAs

et al. 2015

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MicroRNAs (miRNAs) are non-coding RNAs of ~22 nucleotides in length that regulate gene expression by interfering with the stability and translation of mRNAs. Their expression is regulated during development, under a wide variety of stress conditions and in several pathological processes. In nature, animals often face feast or famine conditions. We observed that subjecting early L4 larvae from Caenorhabditis elegans to a 12-hr starvation period produced worms that are thinner and shorter than well-fed animals, with a decreased lipid accumulation, diminished progeny, reduced gonad size, and an increased lifespan. Our objective was to identify which of the 302 known miRNAs of C. elegans changed their expression under starvation conditions as compared to well-fed worms by means of deep sequencing in early L4 larvae. Our results indicate that 13 miRNAs (miR-34-3p, the family of miR-35-3p to miR-41-3p, miR-39-5p, miR-41-5p, miR-240-5p, miR-246-3p and miR-4813-5p) were upregulated, while 2 miRNAs (let-7-3p and miR-85-5p) were downregulated in 12-hr starved vs. well-fed early L4 larvae. Some of the predicted targets of the miRNAs that changed their expression in starvation conditions are involved in metabolic or developmental process. In particular, miRNAs of the miR-35 family were upregulated 6–20 fold upon starvation. Additionally, we showed that the expression of gld-1, important in oogenesis, a validated target of miR-35-3p, was downregulated when the expression of miR-35-3p was upregulated. The expression of another reported target, the cell cycle regulator lin-23, was unchanged during starvation. This study represents a starting point for a more comprehensive understanding of the role of miRNAs during starvation in C. elegans.

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Section: Resultsmentioning

confidence: 99%

High-Throughput Profiling of Caenorhabditis elegans Starvation-Responsive microRNAs

et al. 2015

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“…Next, we used another lin-14 mutant strain lin-14 ( n355n679 ) . n355 is a breakpoint mutation in the 3′UTR of lin-14 , which results in the removal of most of the lin-14 3′UTR, including all the lin-4 and let-7 family miRNA binding sites ( Shi et al 2013 ). In combination with another point mutation ( n679 ) that partially compromises LIN-14 function, the phenotype of lin-14 ( n355n679 ) is similar to lin-4 ( e912 ) ; lin-14 ( n179 ) animals.…”

Section: Resultsmentioning

confidence: 99%

Staufen Negatively Modulates MicroRNA Activity in Caenorhabditis elegans

Ren

Veksler-Lublinsky

Morrissey

et al. 2016

G3 Genes|Genomes|Genetics

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The double-stranded RNA-binding protein Staufen has been implicated in various posttranscriptional gene regulatory processes. Here, we demonstrate that the Caenorhabditis elegans homolog of Staufen, STAU-1, functionally interacts with microRNAs. Loss-of-function mutations of stau-1 significantly suppress phenotypes of let-7 family microRNA mutants, a hypomorphic allele of dicer, and a lsy-6 microRNA partial loss-of-function mutant. Furthermore, STAU-1 modulates the activity of lin-14, a target of lin-4 and let-7 family microRNAs, and this modulation is abolished when the 3′ untranslated region of lin-14 is removed. Deep sequencing of small RNA cDNA libraries reveals no dramatic change in the levels of microRNAs or other small RNA populations between wild-type and stau-1 mutants, with the exception of certain endogenous siRNAs in the WAGO pathway. The modulation of microRNA activity by STAU-1 does not seem to be associated with the previously reported enhanced exogenous RNAi (Eri) phenotype of stau-1 mutants, since eri-1 exhibits the opposite effect on microRNA activity. Altogether, our results suggest that STAU-1 negatively modulates microRNA activity downstream of microRNA biogenesis, possibly by competing with microRNAs for binding on the 3′ untranslated region of target mRNAs.

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“…Analysis of lin-14 mRNA and protein levels over the course of early larval development in wild-type worms has revealed a biphasic mode of regulation: a fast lin-14 mRNA destabilization, as soon as lin-4 miRNA is expressed in mid-L1 stage and a subsequent long-term translational inhibition with reduced LIN-14 protein levels and no obvious further decline in mRNA levels [26]. Here, in a time frame from 0 to 24 h post-embryonic development at 27.5°C, we have observed a similar early destabilization of lin-14 mRNA in wild-type worms, but not in dcap-1 mutants, where a persistent stabilization of mRNA was demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Neuronal function of the mRNA decapping complex determines survival ofCaenorhabditis elegansat high temperature through temporal regulation of heterochronic gene expression

et al. 2017

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In response to adverse environmental cues, Caenorhabditis elegans larvae can temporarily arrest development at the second moult and form dauers, a diapause stage that allows for long-term survival. This process is largely regulated by certain evolutionarily conserved signal transduction pathways, but it is also affected by miRNA-mediated post-transcriptional control of gene expression. The 5′–3′ mRNA decay mechanism contributes to miRNA-mediated silencing of target mRNAs in many organisms but how it affects developmental decisions during normal or stress conditions is largely unknown. Here, we show that loss of the mRNA decapping complex activity acting in the 5′–3′ mRNA decay pathway inhibits dauer formation at the stressful high temperature of 27.5°C, and instead promotes early developmental arrest. Our genetic data suggest that this arrest phenotype correlates with dysregulation of heterochronic gene expression and an aberrant stabilization of lin-14 mRNA at early larval stages. Restoration of neuronal dcap-1 activity was sufficient to rescue growth phenotypes of dcap-1 mutants at both high and normal temperatures, implying the involvement of common developmental timing mechanisms. Our work unveils the crucial role of 5′–3′ mRNA degradation in proper regulation of heterochronic gene expression programmes, which proved to be essential for survival under stressful conditions.

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Dual Regulation of the lin-14 Target mRNA by the lin-4 miRNA

Cited by 10 publications

References 26 publications

High-Throughput Profiling of Caenorhabditis elegans Starvation-Responsive microRNAs

High-Throughput Profiling of Caenorhabditis elegans Starvation-Responsive microRNAs

Staufen Negatively Modulates MicroRNA Activity in Caenorhabditis elegans

Neuronal function of the mRNA decapping complex determines survival ofCaenorhabditis elegansat high temperature through temporal regulation of heterochronic gene expression

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