An essential role for the piRNA pathway in regulating the ribosomal RNA pool in C. elegans

Wahba, Lamia; Hansen, Larry G.; Fire, Andrew

doi:10.1016/j.devcel.2021.07.014

Cited by 36 publications

(56 citation statements)

References 167 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Guang and colleagues characterized this new class of antisense ribosomal siRNAs (risiRNAs) earlier and had shown that they inhibit rRNA expression via the nuclear RNAi pathway (reviewed in [ 59 ]). Importantly, copy-number amplification of rDNA delayed the onset of sterility in piRNA-depleted worms supporting the causal role of impaired ribosome function in the Mrt phenotype [ 58 ].…”

Section: Permanent and Limited Forms Of Tei And Their Genetic Controlmentioning

confidence: 97%

“…Both the de-repression of normally silenced repetitive elements [ 52 ] and the inappropriate silencing of essential endogenous genes, such as histones [ 56 , 57 ], were correlated with the Mrt phenotype. A very recent study by Fire and co-workers identified enhanced production of small RNAs antisense to rRNA as a likely cause of the Mrt phenotypes in animals lacking piRNAs [ 58 ]. Guang and colleagues characterized this new class of antisense ribosomal siRNAs (risiRNAs) earlier and had shown that they inhibit rRNA expression via the nuclear RNAi pathway (reviewed in [ 59 ]).…”

Section: Permanent and Limited Forms Of Tei And Their Genetic Controlmentioning

confidence: 99%

See 1 more Smart Citation

Small RNAs Worm Up Transgenerational Epigenetics Research

Grishok

2021

DNA

View full text Add to dashboard Cite

DNA is central to the propagation and evolution of most living organisms due to the essential process of its self-replication. Yet it also encodes factors that permit epigenetic (not included in DNA sequence) flow of information from parents to their offspring and beyond. The known mechanisms of epigenetic inheritance include chemical modifications of DNA and chromatin, as well as regulatory RNAs. All these factors can modulate gene expression programs in the ensuing generations. The nematode Caenorhabditis elegans is recognized as a pioneer organism in transgenerational epigenetic inheritance research. Recent advances in C. elegans epigenetics include the discoveries of control mechanisms that limit the duration of RNA-based epigenetic inheritance, periodic DNA motifs that counteract epigenetic silencing establishment, new mechanistic insights into epigenetic inheritance carried by sperm, and the tantalizing examples of inheritance of sensory experiences. This review aims to highlight new findings in epigenetics research in C. elegans with the main focus on transgenerational epigenetic phenomena dependent on small RNAs.

show abstract

Section: Permanent and Limited Forms Of Tei And Their Genetic Controlmentioning

confidence: 97%

Section: Permanent and Limited Forms Of Tei And Their Genetic Controlmentioning

confidence: 99%

Small RNAs Worm Up Transgenerational Epigenetics Research

Grishok

2021

DNA

View full text Add to dashboard Cite

show abstract

“…Moreover, mutants defective in piRNA function became gradually sterile due to abnormal accumulation of ribosomal siRNAs that lead to RNAi mediated gene silencing of rRNAs. [20] Therefore, the Mrt phenotype in piRNA mutants could be suppressed by inactivation of nuclear RNAi factor hrde-1. hrde-1 mutation, however, did not suppress the Mrt phenotype in endu-2(lf) mutant, implicating that ENDU-2 probably acts independent of piRNA pathway to preserve germline immortality.…”

Section: Somatic Cells Ensure Germline Immortality Via Secreted Endu-2mentioning

confidence: 99%

Protection of germline immortality by the soma via a secreted endoribonuclease

Baumeister

2021

BioEssays

View full text Add to dashboard Cite

In sexually reproducing organisms maintenance of germ stem cell immortality is fundamental for transmitting genetic material to future generations. While previous research has mainly considered intrinsic regulatory mechanisms in the germline, our recent study has found a direct contribution of somatic cells in preserving germline immortality via the somatically expressed endoribonuclease ENDU-2 in Caenorhabditis elegans. We have identified ENDU-2 as a secreted protein that can be taken up by the germline. Here, we discuss how ENDU-2 might uncouple its RNA-binding and RNAcleavage activities to control gene expression via either an endoribonuclease dependent or an independent way. We also speculate on a possible functional conservation of its mammalian homologs in mediating cell-cell communication as well as its potential significance in understanding human pathogenesis such as cancer development.

show abstract

“…Worms lacking active piRNA pathway are superficially normal but gradually become sterile over several generations as the germline loses its immortal nature (3,4,9,11,12). Contrastingly, depletion of XRN-2 through RNAi results in immediate sterility of the worms (P0) undergoing the treatment, which indicates that apart from contributing in piRNA biogenesis, it plays additional roles that might be critical for germline metabolism.…”

Section: Xrn-2 Depletion Affects Pirna-dependent and Independent Endo-sirnas As Well As Genome Integritymentioning

confidence: 99%

“…22G-RNAs can be transmitted transgenerationally and as a result, silencing of the targets by piRNA pathway can become stable and maintained across several generations, even in the absence of active 21U-RNA-PRG-1 (7). Accordingly, prg-1 mutant worms that lack mature piRNAs, do not become sterile immediately, rather, they show gradual decline in the brood size across generations and eventually become completely sterile after several generations (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Biogenesis of mature piRNAs in Caenorhabditis elegans is dependent on orchestration between multiple ribonucleases and PRG-1

Samajdar

Chowdhury

Chatterjee

2021

Preprint

View full text Add to dashboard Cite

Piwi-interacting RNAs (piRNAs) are an animal-specific class of germline-enriched small non-coding RNAs that shape transcriptome, as well as ensure genomic integrity and fertility by regulating transposons and other selfish genetic elements. In Caenorhabditis elegans mature piRNAs are 21-nucleotides long, begin with a monophosphorylated uridine, and they associate with PRG-1 to form piRISCs that scan the transcriptome for non-self sequences. However, these piRNAs are born as longer 5-capped transcripts, where PARN-1, a 3-5 exoribonuclease, contributes to the formation of the mature 3-end. But, till date, the 5-processing events remain elusive. We demonstrate that the recently identified endoribonuclease activity of XRN-2 is involved in the processing of the 5-end of precursor piRNAs in worms. Depletion of XRN-2 results in reduced mature piRNA levels, with concomitant increase in levels of the 5-capped precursors. We also reveal that the piRNAs born as longer precursor molecules (>60 nt), prior to 5-end processing, undergo ENDU-1-mediated endoribonucleolytic processing of their 3-ends. Our in vitro RNA-protein interaction studies unravel the mechanistic interactions between XRN-2 and PRG-1 towards the formation of mature 5-ends of piRNAs. In vivo experiments employing prg-1 mutant worms indicate that XRN-2 has the potential to perform clearance of precursors that are not bound and protected by PRG-1. Finally, we also demonstrate that XRN-2 is not only important for the generation of mature piRNAs and piRNA-dependent endo-siRNAs, but through yet unknown pathways, it also affects piRNA-independent endo-siRNAs that shape transcriptome, as well as contribute to genomic integrity via regulation of transposable elements.

show abstract

An essential role for the piRNA pathway in regulating the ribosomal RNA pool in C. elegans

Cited by 36 publications

References 167 publications

Small RNAs Worm Up Transgenerational Epigenetics Research

Small RNAs Worm Up Transgenerational Epigenetics Research

Protection of germline immortality by the soma via a secreted endoribonuclease

Biogenesis of mature piRNAs in Caenorhabditis elegans is dependent on orchestration between multiple ribonucleases and PRG-1

Contact Info

Product

Resources

About