Comparative Epigenomics Reveals that RNA Polymerase II Pausing and Chromatin Domain Organization Control Nematode piRNA Biogenesis

Beltran, Toni; Barroso, Consuelo; Birkle, T. Y.; Stevens, Lewis; Schwartz, Hillel T.; Sternberg, Paul W.; Fradin, Hélène; Gunsalus, Kristin C.; Piano, Fabio; Sharma, Garima; Cerrato, Chiara; Ahringer, Julie; Martínez-Pérez, Enrique; Blaxter, Mark; Sarkies, Peter

doi:10.1016/j.devcel.2018.12.026

Cited by 44 publications

(86 citation statements)

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“…Two large clusters of piRNAs are found in C. elegans on chromosome IV (Ruby et al, 2006), while clustering of piRNA loci is not observed in P. pacificus (de Wit et al, 2009) nor in H. contortus (Winter et al, 2012). Recent work by Beltran et al (2019) also identified differences in the chromatin structure of domains encoding piRNAs between nematode species, suggesting different modes of regulation. Two types of genomic organization of piRNA genes were characterized: P-type (e.g.…”

Section: Nematode Pirnasmentioning

confidence: 97%

Small RNAs in parasitic nematodes – forms and functions

2019

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Small RNAs are important regulators of gene expression. They were first identified in Caenorhabditis elegans, but it is now apparent that the main small RNA silencing pathways are functionally conserved across diverse organisms. Availability of genome data for an increasing number of parasitic nematodes has enabled bioinformatic identification of small RNA sequences. Expression of these in different lifecycle stages is revealed by small RNA sequencing and microarray analysis. In this review we describe what is known of the three main small RNA classes in parasitic nematodes – microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs) and small interfering RNAs (siRNAs) – and their proposed functions. miRNAs regulate development in C. elegans and the temporal expression of parasitic nematode miRNAs suggest modulation of target gene levels as parasites develop within the host. miRNAs are also present in extracellular vesicles released by nematodes in vitro, and in plasma from infected hosts, suggesting potential regulation of host gene expression. Roles of piRNAs and siRNAs in suppressing target genes, including transposable elements, are also reviewed. Recent successes in RNAi-mediated gene silencing, and application of small RNA inhibitors and mimics will continue to advance understanding of small RNA functions within the parasite and at the host–parasite interface.

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Section: Nematode Pirnasmentioning

confidence: 97%

Small RNAs in parasitic nematodes – forms and functions

2019

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“…Transcription of these genes requires a protein named PRDE-1 and the transcription factor SNPC-4 (Kasper et al 2014;Weng et al 2018), the latter of which is also known to be involved in transcription of other short structural RNAs, such as snRNAs and splice leader RNAs (Kasper et al 2014). An evolutionary analysis of 21U RNA loci in diverse nematodes has revealed that 21U loci may have evolved from snRNA loci (Beltran et al 2019). These loci include both the strongly conserved U1 and U2 loci as well as loci producing so-called splice leader RNAs (SL1 and SL2) that are trans-spliced to the 5 ′ ends of a large fraction of all mRNAs in C. elegans (Blumenthal 2012).…”

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confidence: 99%

PETISCO is a novel protein complex required for 21U RNA biogenesis and embryonic viability

et al. 2019

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Piwi proteins are important for germ cell development in most animals. These proteins are guided to specific targets by small guide RNAs, referred to as piRNAs or 21U RNAs in Caenorhabditis elegans. In this organism, even though genetic screens have uncovered 21U RNA biogenesis factors, little is known about how these factors interact or what they do. Based on the previously identified 21U biogenesis factor PID-1 (piRNA-induced silencing-defective 1), we here define a novel protein complex, PETISCO (PID-3, ERH-2, TOFU-6, and IFE-3 small RNA complex), that is required for 21U RNA biogenesis. PETISCO contains both potential 5 ′ cap and 5 ′ phosphate RNA-binding domains and interacts with capped 21U precursor RNA. We resolved the architecture of PETISCO and revealed a second function for PETISCO in embryonic development. This essential function of PETISCO is mediated not by PID-1 but by the novel protein TOST-1 (twenty-one U pathway antagonist). In contrast, TOST-1 is not essential for 21U RNA biogenesis. Both PID-1 and TOST-1 interact directly with ERH-2 using a conserved sequence motif. Finally, our data suggest a role for TOST-1:PETISCO in SL1 homeostasis in the early embryo. Our work describes a key complex for 21U RNA processing in C. elegans and strengthens the view that 21U RNA biogenesis is built on an snRNA-related pathway.

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“…Perhaps RPB-9 is part of an ancient network which, together with SNPC-4 (Kasper et al, 2014) and the USTC complex , has been recruited to direct transcription at piRNA loci. The recent discovery that motif-dependent piRNA units share evolutionary similarities with the highly conserved snRNA genes (Beltran et al, 2019) , together with the fact that transcription of both these types of loci depends on the Integrator complex (Baillat et al, 2005;Ezzeddine et al, 2011Ezzeddine et al, , 2012Uguen and Murphy, 2003) (Beltran et al, 2020 co-submitted), seem to favor this hypothesis. Whether rpb-9 is required for transcription of snRNA genes in C. elegans is however currently unknown.…”

Section: Discussionmentioning

confidence: 99%

“…At non polyadenylated-type loci, such as those encoding for small nuclear RNAs (snRNAs), termination depends on specialized processing of the 3′ ends and often requires the Integrator complex, whose nuclease activity at specific cleavage sites is necessary for precursor transcript maturation (Baillat et al, 2005;Ezzeddine et al, 2011Ezzeddine et al, , 2012Uguen and Murphy, 2003) . Interestingly, transcription at motif-dependent piRNA loci shares evolutionary similarities to snRNA transcription (Beltran et al, 2019) .…”

Section: Introductionmentioning

confidence: 99%

The RNA Polymerase II core subunit RPB-9 directs transcriptional elongation at piRNA loci inCaenorhabditis elegans

Berkyurek

Furlan

Lampersberger

et al. 2020

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These authors contributed equally % Corresponding author: Eric A Miska: eam29@cam.ac.uk, +44-1223-334088, https://orcid.org/0000-0002-4450-576X 1 Manuscript ABSTRACT PIWI-interacting RNAs (piRNAs) are genome-encoded small RNAs that regulate germ cell development and maintain germline integrity in many animals. Mature piRNAs engage Piwi Argonaute proteins to silence complementary transcripts, including transposable elements and endogenous genes. piRNA biogenesis mechanisms are diverse and remain poorly understood. Here, we identify the RNA Polymerase II (RNA Pol II) core subunit RPB-9 as required for piRNA-mediated silencing in the nematodeCaenorhabditis elegans . rpb-9 mutants fail to initiate heritable piRNA-mediated gene silencing. Furthermore, we show that RPB-9 is required to repress two DNA transposon families and a subset of somatic genes in the C. elegans germline. We provide genetic and biochemical evidence that RPB-9 is required for piRNA biogenesis. We demonstrate that RPB-9 acts to promote transcriptional elongation/termination at endogenous piRNA loci. We conclude that as a part of its rapid evolution the piRNA pathway has co-opted another ancient machinery, this time for high-fidelity transcription.al., 2019) at the Ruby motif. Transcribed piRNA precursors are 26 to 29 nucleotides (nt) in length and carry a 5′ 7-methylguanylate cap (Goh et al., 2014;Gu et al., 2012;Weick et al., 2014) . After transcription, precursors are promptly exported out of the nucleus, possibly by PID-1 (de Albuquerque et al., 2014) , which is predicted to have both nuclear localization and export signals, and later bound by the PETISCO/PICS complexes (Cordeiro Rodrigues et al., 2019;Zeng et al., 2019) , which might be involved in 5′ end precursor processing, including decapping and 5′ end trimming. Subsequent 3′-end trimming is mediated by the exonuclease PARN-1 (Tang et al., 2016) . The resulting mature C. elegans piRNAs are 21 nt small RNAs with a 5′ uracil bias (hence called 21U-RNAs). They also possess a 5′ monophosphate and a 3′ hydroxyl group at their extremities, and are post-transcriptionally 2′-O methylated at the 3′ end by the HENN-1 enzyme (Kamminga et al., 2010;Montgomery et al., 2012) .Mature piRNAs bind to PIWI subfamily proteins of the AGO family and guide them to complementary target transcripts. Two PIWI proteins with germline-restricted expression, PRG-1 and PRG-2, have been identified in C. elegans , although only PRG-1 is required for maintaining wild-type piRNA populations (Batista et al., 2008;Das et al., 2008;Wang and Reinke, 2008) . These proteins localize to P-granules, specialized germline-specific phase-separated perinuclear structures that are the main site of piRNA-mediated post-transcriptional gene silencing activities (Updike and Strome, 2010) .Unlike in other animals, where PIWI/piRNA complexes can silence their targets via a PIWI endonuclease "slicing" activity, PRG-1/piRNA complexes in C. elegans silence their targets by triggering their degradation indirectly. The imperfect base pairing ...

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Comparative Epigenomics Reveals that RNA Polymerase II Pausing and Chromatin Domain Organization Control Nematode piRNA Biogenesis

Cited by 44 publications

References 70 publications

Small RNAs in parasitic nematodes – forms and functions

Small RNAs in parasitic nematodes – forms and functions

PETISCO is a novel protein complex required for 21U RNA biogenesis and embryonic viability

The RNA Polymerase II core subunit RPB-9 directs transcriptional elongation at piRNA loci inCaenorhabditis elegans

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