Distinct Phases of siRNA Synthesis in an Endogenous RNAi Pathway in C. elegans Soma

Gent, Jonathan I.; Lamm, Ayelet T.; Pavelec, Derek M.; Maniar, Jay M.; Parameswaran, Poornima; Li, Tao; Kennedy, Scott; Fire, Andrew

doi:10.1016/j.molcel.2010.01.012

Cited by 179 publications

(265 citation statements)

References 59 publications

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“…S7B; Supplemental Table S7) (sequence data were obtained from GEO, accession: GSE20649) (Corrêa et al 2010). A similar reduction of miRNA star level in rde-1 mutants was also observed in another library obtained from the GEO, GSE19414 (Gent et al 2010) (data not shown). These results suggest that the star miRNA strands are preferentially sorted into or stabilized in RDE-1 Argonaute protein in C. elegans.…”

Section: Resultssupporting

confidence: 61%

Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans

Kato¹,

Chen²,

Inukai³

et al. 2011

RNA

152

154

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Small, noncoding RNAs (sncRNAs), including microRNAs (miRNAs), impact diverse biological events through the control of gene expression and genome stability. However, the role of these sncRNAs in aging remains largely unknown. To understand the contribution of sncRNAs to the aging process, we performed small RNA profiling by deep-sequencing over the course of Caenorhabditis elegans (C. elegans) aging. Many small RNAs, including a significant number of miRNAs, change their expression during aging in C. elegans. Further studies of miRNA expression changes under conditions that modify lifespan demonstrate the tight control of their expression during aging. Adult-specific loss of argonaute-like gene-1 (alg-1) activity, which is necessary for miRNA maturation and function, resulted in an abnormal lifespan, suggesting that miRNAs are, indeed, required in adulthood for normal aging. miRNA target prediction algorithms combined with transcriptome data and pathway enrichment analysis revealed likely targets of these age-associated miRNAs with known roles in aging, such as mitochondrial metabolism. Furthermore, a computational analysis of our deep-sequencing data identified additional age-associated sncRNAs, including miRNA star strands, novel miRNA candidates, and endo-siRNA sequences. We also show an increase of specific transfer RNA (tRNA) fragments during aging, which are known to be induced in response to stress in several organisms. This study suggests that sncRNAs including miRNAs contribute to lifespan regulation in C. elegans, and indicates new connections between aging, stress responses, and the small RNA world.

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Section: Resultssupporting

confidence: 61%

Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans

Kato¹,

Chen²,

Inukai³

et al. 2011

RNA

152

154

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“…There are four RdRPs in C. elegans: RRF-3 functions in the production of 26G siRNAs (Gent et al 2010), EGO-1 and RRF-1 have partially overlapping roles in 22G siRNA formation ), and RRF-2, which is closely related to RRF-1, has an unknown role (Sijen et al 2001). From a phylogenetic analysis of nematode RdRPs, we identified likely orthologs of the three RdRP subfamilies, RRF-1, RRF-3, and EGO-1 in each of the other three nematode species (Fig.…”

Section: Resultsmentioning

confidence: 99%

High-throughput sequencing reveals extraordinary fluidity of miRNA, piRNA, and siRNA pathways in nematodes

Shi

Montgomery

et al. 2013

Genome Res.

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The nematode Caenorhabditis elegans contains each of the broad classes of eukaryotic small RNAs, including microRNAs (miRNAs), endogenous small-interfering RNAs (endo-siRNAs), and piwi-interacting RNAs (piRNAs). To better understand the evolution of these regulatory RNAs, we deep-sequenced small RNAs from C. elegans and three closely related nematodes: C. briggsae, C. remanei, and C. brenneri. The results reveal a fluid landscape of small RNA pathways with essentially no conservation of individual sequences aside from a subset of miRNAs. We identified 54 miRNA families that are conserved in each of the four species, as well as numerous miRNAs that are species-specific or shared between only two or three species. Despite a lack of conservation of individual piRNAs and siRNAs, many of the features of each pathway are conserved between the different species. We show that the genomic distribution of 26G siRNAs and the tendency for piRNAs to cluster is conserved between C. briggsae and C. elegans. We also show that, in each species, 26G siRNAs trigger stage-specific secondary siRNA formation. piRNAs in each species also trigger secondary siRNA formation from targets containing up to three mismatches. Finally, we show that the production of male-and female-specific piRNAs is conserved in all four species, suggesting distinct roles for piRNAs in male and female germlines.

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“…These biases could reflect the sequence motifs preferred by RdRPs on mRNA templates for the synthesis of 22G RNAs. Whereas considering all 22-nt RNAs together suggested a modest preference for a C or U immediately upstream of 22-nt RNAs (Gent et al 2010), examining RNAs with different 5 ′ nucleotides separately clarifies the observation and reveals that synthesis of RNAs with 5 ′ nucleotides other than G appear to be promoted by specific upstream bases on mRNA templates.…”

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

confidence: 92%

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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Distinct Phases of siRNA Synthesis in an Endogenous RNAi Pathway in C. elegans Soma

Cited by 179 publications

References 59 publications

Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans

Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans

High-throughput sequencing reveals extraordinary fluidity of miRNA, piRNA, and siRNA pathways in nematodes

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

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