Discovery and Characterization of piRNAs in the Human Fetal Ovary

Williams, Zev; Morozov, Pavel; Mihailović, Aleksandra; Lin, Carolina; Puvvula, Pavan Kumar; Juranek, Stefan; Rosenwaks, Zev; Tuschl, Thomas

doi:10.1016/j.celrep.2015.09.030

Cited by 103 publications

(113 citation statements)

References 67 publications

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…It is possible, however, that presence of several other putative serially N-terminally truncated Mili isoforms (and their serially 5′ truncated transcripts), as postulated (29), may have complicated interpretation of our RNA-Seq data. Although we failed to detect Miwi2 expression by RNA-seq analyses, others have reported expression of its human homolog (piwil4) protein in brain tissues (32). We suspect that our failure to detect Miwi2 transcript in our RNA-Seq analyses could either be due to the instability of Miwi2 mRNA or to the lack of sequencing depth.…”

Section: Resultscontrasting

confidence: 43%

“…S3B). Further characterization of potential piRNAs by mapping non-miRNA, nonstructural RNA, and non-repeat-derived reads to National Center for Biotechnology Information (NCBI) Refseq and by requiring size specification (26-32 nt) together with a starting uridine base (5′U), failed to find evidence for gene-derived piRNAs (1,32) (Fig. S4).…”

Section: Retrotransposon-derived Small Rnas With Pirna-like Features Arementioning

confidence: 99%

See 1 more Smart Citation

Roles for small noncoding RNAs in silencing of retrotransposons in the mammalian brain

Nandi

Chandramohan

Fioriti

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Piwi-interacting RNAs (piRNAs), long thought to be restricted to germline, have recently been discovered in neurons of Aplysia, with a role in the epigenetic regulation of gene expression underlying long-term memory. We here ask whether piwi/piRNAs are also expressed and have functional roles in the mammalian brain. Large-scale RNA sequencing and subsequent analysis of protein expression revealed the presence in brain of several piRNA biogenesis factors including a mouse piwi (Mili), as well as small RNAs, albeit at low levels, resembling conserved piRNAs in mouse testes [primarily LINE1 (long interspersed nuclear element1) retrotransposon-derived]. Despite the seeming low expression of these putative piRNAs, single-base pair CpG methylation analyses across the genome of Mili/piRNA-deficient (Mili −/− ) mice demonstrate that brain genomic DNA is preferentially hypomethylated within intergenic areas and LINE1 promoter areas of the genome. Furthermore, Mili mutant mice exhibit behavioral deficits such as hyperactivity and reduced anxiety. These results suggest that putative piRNAs exist in mammalian brain, and similar to the role of piRNAs in testes, they may be involved in the silencing of retrotransposons, which in brain have critical roles in contributing to genomic heterogeneity underlying adaptation, stress response, and brain pathology. We also describe the presence of another class of small RNAs in the brain, with features of endogenous siRNAs, which may have taken over the role of invertebrate piRNAs in their capacity to target both transposons, as well as protein-coding genes. Thus, RNA interference through gene and retrotransposon silencing previously encountered in Aplysia may also have potential roles in the mammalian brain.piwi-interacting RNA | transposon | DNA methylation | behavior | endogenous siRNA P iwi-interacting RNAs (piRNAs) are 26-to 32-nt small noncoding RNAs that associate with the piwi clade of the Argonaute family of proteins and whose primary functions in mammals are associated with the silencing of transposons in the germline through de novo DNA methylation (1-4). Transposons constitute 44% of the human genome and could when active contribute to genetic heterogeneity, to alteration of behavior during adaptation, and to responses to stress. Somatic retrotransposition and its associated insertional mutagenesis have particularly important implications for brain disorders and are often associated with schizophrenia, Rett syndrome, and neurodegenerative disorders (5-7). The LINE1 (long interspersed nuclear element1) family of retrotransposons in particular is active in human and mouse hippocampus (8, 9).Although it has long been thought that piRNA expression and function are restricted to the germline, our laboratory and others have previously found that the piRNA pathway is functional in invertebrate neurons as well (10, 11). Aplysia neurons, in particular, have a strikingly abundant expression of piRNAs (contributing to at least 5% of the total noncoding RNA population); they in turn hav...

show abstract

Section: Resultscontrasting

confidence: 43%

Section: Retrotransposon-derived Small Rnas With Pirna-like Features Arementioning

confidence: 99%

Roles for small noncoding RNAs in silencing of retrotransposons in the mammalian brain

Nandi

Chandramohan

Fioriti

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Though earlier work established that piRNA pathway features are conserved between humans and other mammals (Aravin et al 2006;Girard et al 2006;Yang et al 2013;Ha et al 2014;Roovers et al 2015;Rosenkranz et al 2015a;Rounge et al 2015;Williams et al 2015), due to ethical and technical limitations, research progress in humans has been slower. Specifically, while all postnatal human piRNAs were previously mapped to piRNA clusters (Ha et al 2014;Roovers et al 2015;Rosenkranz et al 2015a;Williams et al 2015), these clusters were ill-defined in the genome.…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, while all postnatal human piRNAs were previously mapped to piRNA clusters (Ha et al 2014;Roovers et al 2015;Rosenkranz et al 2015a;Williams et al 2015), these clusters were ill-defined in the genome. Also, no prior study has performed a thorough analysis of TE targeting by the piRNA pathway at different stages of spermatogenesis (i.e., prenatal and postnatal).…”

Section: Introductionmentioning

confidence: 99%

Two modes of targeting transposable elements by piRNA pathway in human testis

Gainetdinov

Skvortsova

Kondratieva

et al. 2017

RNA

View full text Add to dashboard Cite

PIWI proteins and their partner small RNAs, termed piRNAs, are known to control transposable elements (TEs) in the germline. Here, we provide evidence that in humans this control is exerted in two different modes. On the one hand, production of piRNAs specifically targeting evolutionarily youngest TEs (L1HS, L1PA2-L1PA6, LTR12C, SVA) is present both at prenatal and postnatal stages of spermatogenesis and is performed without involvement of piRNA clusters. On the other hand, at postnatal stages, piRNAs deriving from pachytene clusters target "older" TEs and thus complement cluster-independent piRNA production to achieve relevant targeting of virtually all TEs expressed in postnatal testis. We also find that converging transcription of antisense-oriented genes contributes to the origin of genic postnatal prepachytene clusters. Finally, while a fraction of pachytene piRNAs was previously shown to arise from long intergenic noncoding RNAs (lincRNAs, i.e., pachytene piRNA cluster primary transcripts), we ascertain that these are a specific set of lincRNAs that both possess distinguishing epigenetic features and are expressed exclusively in testis.

show abstract

“…PiRNAs are believed to be involved in germ cell formation by post-transcriptional silencing of retrotransposons and mRNAs in reproductive organs (Watanabe et al 2006(Watanabe et al , 2011Kuramochi-Miyagawa et al 2008;Gou et al 2014, Williams et al 2015 3. Endogenous or synthetically produced short interfering RNAs (siRNAs; doublestranded, 20-24 nt).…”

Section: Introductionmentioning

confidence: 99%

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop

Aigner¹,

Buesen²,

Gant³

et al. 2016

Regulatory Toxicology and Pharmacology

View full text Add to dashboard Cite

The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that the abundance of data obtained from ncRNA expression profiling requires careful evaluation to determine the utility of specific ncRNAs for regulatory toxicology. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify candidate ncRNAs for further assessment as potential biomarkers of toxicity and areas of toxicology where ncRNA expression profiling can address prevailing scientific deficiencies.(2) Develop consensus on how to conduct and report ncRNA expression profiling in a toxicological context to support applicability for regulatory decision-making. (3) Conduct experimental projects to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. As necessary, retrospective analyses (e.g. from surplus samples from control groups from regulatory studies) can be supplemented with new (90-day) rat oral toxicity studies. These projects should aim at establishing physiological ncRNA expression profiles including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be linked with substance-induced apical effects in a dose-dependent manner. Applying a holistic approach, knowledge on ncRNAs, and relevant information from 'omics and epigenetics technologies, should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context.

show abstract

Discovery and Characterization of piRNAs in the Human Fetal Ovary

Cited by 103 publications

References 67 publications

Roles for small noncoding RNAs in silencing of retrotransposons in the mammalian brain

Roles for small noncoding RNAs in silencing of retrotransposons in the mammalian brain

Two modes of targeting transposable elements by piRNA pathway in human testis

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop

Contact Info

Product

Resources

About