Unusual DNA Structures Associated With Germline Genetic Activity in <i>Caenorhabditis elegans</i>

Fire, Andrew; Alcazar, Rosa; Tan, Frederick J.

doi:10.1534/genetics.106.057364

Cited by 64 publications

(81 citation statements)

References 82 publications

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“…The let-858 promoter drives ubiquitous expression and in the past this promoter has provided for transcriptional activity of transgenes in the germline, a tissue that normally silences transgene expression (Kelly et al 1997;Fire et al 2006;Sundaram et al 2006). Using this approach, we observed RNAi activity in rsd-2 mutants that ectopically expressed RSD-2 or RSD-2TGFP fusion proteins from transgenes that were maintained as extrachromosomal arrays ( Figure 2B and Table 1).…”

Section: Resultsmentioning

confidence: 86%

TheCaenorhabditis elegans rsd-2andrsd-6Genes Are Required for Chromosome Functions During Exposure to Unfavorable Environments

Sundaram¹,

Kenjale²,

Grantham

et al. 2008

Genetics

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In Caenorhabditis elegans, exogenous dsRNA can elicit systemic RNAi, a process that requires the function of many genes. Considering that the activities of many of these genes are also required for normal development, it is surprising that exposure to high concentrations of dsRNA does not elicit adverse consequences to animals. Here, we report inducible phenotypes in attenuated C. elegans strains reared in environments that include nonspecific dsRNA and elevated temperature. Under these conditions, chromosome integrity is compromised in RNAi-defective strains harboring mutations in rsd-2 or rsd-6. Specifically, rsd-2 mutants display defects in transposon silencing, while meiotic chromosome disjunction is affected in rsd-6 mutants. RSD-2 proteins localize to multiple cellular compartments, including the nucleolus and cytoplasmic compartments that, in part, are congruent with calreticulin and HAF-6. We considered that the RNAi defects in rsd-2 mutants might have relevance to membrane-associated functions; however, endomembrane compartmentalization and endocytosis/exocytosis markers in rsd-2 and rsd-6 mutants appear normal. The mutants also possess environmentally sensitive defects in cellautonomous RNAi elicited from transgene-delivered dsRNAs. Thus, the ultimate functions of rsd-2 and rsd-6 in systemic RNAi are remarkably complex and environmentally responsive.

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Section: Resultsmentioning

confidence: 86%

TheCaenorhabditis elegans rsd-2andrsd-6Genes Are Required for Chromosome Functions During Exposure to Unfavorable Environments

Sundaram¹,

Kenjale²,

Grantham

et al. 2008

Genetics

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“…1C, right) that were detectable above the background sequence bias in the C. elegans genome (Fig. 1C, left;Fire et al 2006) in all three data sets. The biases detected 1 nt upstream of the 5 ′ end of the RNA depended on the identity of the 5 ′ base of the 22-nt RNA (Fig.…”

Section: G Rnas and Their Derivatives Are Made From Characteristic mentioning

confidence: 84%

Reproducible features of small RNAs in C. elegans reveal NU RNAs and provide insights into 22G RNAs and 26G RNAs

Blumenfeld

Jose

2015

RNA

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Small RNAs regulate gene expression and most genes in the worm Caenorhabditis elegans are subject to their regulation. Here, we analyze small RNA data sets and use reproducible features of RNAs present in multiple data sets to discover a new class of small RNAs and to reveal insights into two known classes of small RNAs-22G RNAs and 26G RNAs. We found that reproducibly detected 22-nt RNAs, although are predominantly RNAs with a G at the 5 ′ end, also include RNAs with A, C, or U at the 5 ′ end. These RNAs are synthesized downstream from characteristic sequence motifs on mRNA and have U-tailed derivatives. Analysis of 26G RNAs revealed that they are processed from a blunt end of double-stranded RNAs and that production of one 26G RNA generates a hotspot immediately downstream for production of another. To our surprise, analysis of RNAs shorter than 18 nt revealed a new class of RNAs, which we call NU RNAs (pronounced "new RNAs") because they have a NU bias at the 5 ′ end, where N is any nucleotide. NU RNAs are antisense to genes and originate downstream from U bases on mRNA. Although many genes have complementary NU RNAs, their genome-wide distribution is distinct from that of previously known classes of small RNAs. Our results suggest that current approaches underestimate reproducibly detected RNAs that are shorter than 18 nt, and theoretical considerations suggest that such shorter RNAs could be used for sequence-specific gene regulation in organisms like C. elegans that have small genomes.

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“…This region binds to the zinc-finger protein HIM-8 and associates with the nuclear envelope during meiotic prophase . The left end of the X is also enriched relative to the rest of the X chromosome for AA/TT dinucleotides that are periodically spaced along one face of the DNA helix, and that may influence DNA bending and chromatin structure (Fire et al, 2006). The X-chromosome left end also contains three copies of a 14 base pair perfect repeat that is distributed abundantly over the autosomes (696 copies total), but found nowhere else on the X chromosome (I.…”

Section: H3k36me2 Marks May Serve Diverse Rolesmentioning

confidence: 99%

MES-4: an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in theC. elegansgerm line

et al. 2006

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Germ cell development in C. elegans requires that the X chromosomes be globally silenced during mitosis and early meiosis. We previously found that the nuclear proteins MES-2, MES-3, MES-4 and MES-6 regulate the different chromatin states of autosomes versus X chromosomes and are required for germline viability. Strikingly, the SET-domain protein MES-4 is concentrated on autosomes and excluded from the X chromosomes. Here, we show that MES-4 has histone H3 methyltransferase (HMT) activity in vitro, and is required for histone H3K36 dimethylation in mitotic and early meiotic germline nuclei and early embryos. MES-4 appears unlinked to transcription elongation, thus distinguishing it from other known H3K36 HMTs. Based on microarray analysis, loss of MES-4 leads to derepression of X-linked genes in the germ line. We discuss how an autosomally associated HMT may participate in silencing genes on the X chromosome, in coordination with the direct silencing effects of the other MES proteins.

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Unusual DNA Structures Associated With Germline Genetic Activity in Caenorhabditis elegans

Cited by 64 publications

References 82 publications

TheCaenorhabditis elegans rsd-2andrsd-6Genes Are Required for Chromosome Functions During Exposure to Unfavorable Environments

TheCaenorhabditis elegans rsd-2andrsd-6Genes Are Required for Chromosome Functions During Exposure to Unfavorable Environments

Reproducible features of small RNAs in C. elegans reveal NU RNAs and provide insights into 22G RNAs and 26G RNAs

MES-4: an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in theC. elegansgerm line

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