scholarly journals Germline inherited small RNAs clear untranslated maternal mRNAs in C. elegans embryos

2020 ◽  
Author(s):  
Piergiuseppe Quarato ◽  
Meetali Singh ◽  
Eric Cornes ◽  
Blaise Li ◽  
Loan Bourdon ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Embryonic Development ◽  
Small Rnas ◽  
Dependent Manner ◽  
C Elegans ◽  
Mrna Targets ◽  
Maternal To Zygotic Transition ◽  
Catalytically Active ◽  
Maternal Mrnas ◽  
Non Coding Rnas

ABSTRACTInheritance and clearance of maternal mRNAs are two of the most critical events required for animal early embryonic development. However, the mechanisms regulating this process are still largely unknown. Here, we show that together with maternal mRNAs, C. elegans embryos inherit a complementary pool of small non-coding RNAs capable of triggering the cleavage and removal of hundreds of maternal mRNAs. These antisense small RNAs are loaded into the maternal catalytically-active Argonaute CSR-1 and cleave complementary mRNAs no longer engaged in translation in somatic blastomeres. Induced depletion of CSR-1 specifically during embryonic development leads to embryonic lethality in a slicer-dependent manner and impairs the degradation of CSR-1 embryonic mRNA targets. Given the conservation of Argonaute catalytic activity, we propose that a similar mechanism operates to clear maternal mRNAs during the maternal-to-zygotic transition across species.

scholarly journals Germline inherited small RNAs facilitate the clearance of untranslated maternal mRNAs in C. elegans embryos

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Piergiuseppe Quarato ◽  
Meetali Singh ◽  
Eric Cornes ◽  
Blaise Li ◽  
Loan Bourdon ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Embryonic Development ◽  
Small Rnas ◽  
Dependent Manner ◽  
C Elegans ◽  
Mrna Targets ◽  
Maternal To Zygotic Transition ◽  
Catalytically Active ◽  
Maternal Mrnas ◽  
Non Coding Rnas

AbstractInheritance and clearance of maternal mRNAs are two of the most critical events required for animal early embryonic development. However, the mechanisms regulating this process are still largely unknown. Here, we show that together with maternal mRNAs,C. elegansembryos inherit a complementary pool of small non-coding RNAs that facilitate the cleavage and removal of hundreds of maternal mRNAs. These antisense small RNAs are loaded into the maternal catalytically-active Argonaute CSR-1 and cleave complementary mRNAs no longer engaged in translation in somatic blastomeres. Induced depletion of CSR-1 specifically during embryonic development leads to embryonic lethality in a slicer-dependent manner and impairs the degradation of CSR-1 embryonic mRNA targets. Given the conservation of Argonaute catalytic activity, we propose that a similar mechanism operates to clear maternal mRNAs during the maternal-to-zygotic transition across species.

Label-free proteomic analysis reveals large dynamic changes to the cellular proteome upon expression of the miRNA-23a-27a-24-2 microRNA cluster

2020 ◽  
Vol 98 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Ramanaguru S. Piragasam ◽  
S. Faraz Hussain ◽  
Steven G. Chaulk ◽  
Zaeem A. Siddiqi ◽  
Richard P. Fahlman
Keyword(s):  
Gene Expression ◽  
Proteomic Analysis ◽  
Small Rnas ◽  
Regulatory Networks ◽  
Mirna Cluster ◽  
Label Free ◽  
Dynamic Changes ◽  
Mrna Targets ◽  
Order Of Magnitude ◽  
Non Coding Rnas

In deciphering the regulatory networks of gene expression controlled by the small non-coding RNAs known as microRNAs (miRNAs), a major challenge has been with the identification of the true mRNA targets by these RNAs within the context of the enormous numbers of predicted targets for each of these small RNAs. To facilitate the system-wide identification of miRNA targets, a variety of system wide methods, such as proteomics, have been implemented. Here we describe the utilization of quantitative label-free proteomics and bioinformatics to identify the most significant changes to the proteome upon expression of the miR-23a-27a-24-2 miRNA cluster. In light of recent work leading to the hypothesis that only the most pronounced regulatory events by miRNAs may be physiologically relevant, our data reveal that label-free analysis circumvents the limitations of proteomic labeling techniques that limit the maximum differences that can be quantified. The result of our analysis identifies a series of novel candidate targets that are reduced in abundance by more than an order of magnitude upon the expression of the miR-23a-27a-24-2 cluster.

scholarly journals A stress-induced Tyrosine tRNA depletion response mediates codon-based translational repression and growth suppression

2018 ◽  
Author(s):  
Doowon Huh ◽  
Maria C. Passarelli ◽  
Jenny Gao ◽  
Shahnoza N Dusmatova ◽  
Clara Goin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Small Rna ◽  
Small Rnas ◽  
Oxidative Stress Response ◽  
Translational Repression ◽  
Dependent Manner ◽  
Transfer Rnas ◽  
C Elegans ◽  
Metabolic Genes ◽  
Rna Fragments

SUMMARYEukaryotic transfer RNAs can become selectively fragmented upon various stresses, generating tRNA-derived small RNA fragments. Such fragmentation has been reported to impact a small fraction of the tRNA pool and thus presumed to not directly impact translation. We report that oxidative stress can rapidly generate tyrosine tRNAGUA fragments in human cells—causing significant depletion of the precursor tRNA. Tyrosine tRNAGUA depletion impaired translation of growth and metabolic genes enriched in cognate tyrosine codons. Depletion of tyrosine tRNAGUA or its translationally regulated targets USP3 and SCD repressed proliferation—revealing a dedicated tRNA-regulated growth suppressive pathway for oxidative stress response. Tyrosine fragments are generated in a DIS3L2 exoribonuclease-dependent manner and inhibit hnRNPA1-mediated transcript destabilization. Moreover, tyrosine fragmentation is conserved in C. elegans. Thus, tRNA fragmentation can coordinately generate trans-acting small-RNAs and functionally deplete a tRNA. Our findings reveal the existence of an underlying adaptive codon-based regulatory response inherent to the genetic code.

scholarly journals A membrane-associated condensate drives paternal epigenetic inheritance in C. elegans

2020 ◽  
Author(s):  
Jan Schreier ◽  
Sabrina Dietz ◽  
Antonio M. de Jesus Domingues ◽  
Ann-Sophie Seistrup ◽  
Dieu An H. Nguyen ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Small Rnas ◽  
Maternal Inheritance ◽  
Epigenetic Inheritance ◽  
C Elegans ◽  
Intrinsically Disordered ◽  
Regulatory Information ◽  
Intrinsically Disordered Region ◽  
Gene Regulatory ◽  
Non Coding Rnas

SUMMARYTransgenerational epigenetic inheritance (TEI) describes the transmission of gene-regulatory information across generations without altering DNA sequences, and allows priming of offspring towards transposable elements (TEs) and changing environmental conditions. One important mechanism that acts in TEI is based on small non-coding RNAs. Whereas factors for maternal inheritance of small RNAs have been identified, paternal inheritance is poorly understood, as much of the cellular content is extruded during spermatogenesis. We identify a phase separation-based mechanism, driven by the protein PEI-1, which is characterized by a BTB-BACK domain and an intrinsically disordered region (IDR). PEI-1 specifically secures the Argonaute protein WAGO-3 within maturing sperm in C. elegans. Localization of PEI granules in mature sperm is coupled, via S-palmitoylation, to myosin-driven transport of membranous organelles. pei-1-like genes are also found in human and often expressed in testis, suggesting that the here identified mechanism may be broadly conserved.

scholarly journals C. elegans “reads” bacterial non-coding RNAs to learn pathogenic avoidance

2020 ◽  
Author(s):  
Rachel Kaletsky ◽  
Rebecca S. Moore ◽  
Geoffrey D. Vrla ◽  
Lance L. Parsons ◽  
Zemer Gitai ◽  
...  
Keyword(s):  
Small Rnas ◽  
Food Sources ◽  
C Elegans ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Microbial Environment ◽  
Bacterial Small Rna ◽  
Necessary And Sufficient ◽  
Pathogen Avoidance ◽  
Dependent Mechanism

AbstractC. elegans is exposed to many different bacteria in its environment, and must distinguish pathogenic from nutritious bacterial food sources. Here, we show that a single exposure to purified small RNAs isolated from pathogenic Pseudomonas aeruginosa (PA14) is sufficient to induce pathogen avoidance, both in the treated animals and in four subsequent generations of progeny. The RNA interference and piRNA pathways, the germline, and the ASI neuron are required for bacterial small RNA-induced avoidance behavior and transgenerational inheritance. A single non-coding RNA, P11, is both necessary and sufficient to convey learned avoidance of PA14, and its C. elegans target, maco-1, is required for avoidance. A natural microbiome Pseudomonas isolate, GRb0427, can induce avoidance via its small RNAs, and the wild C. elegans strain JU1580 responds similarly to bacterial sRNA. Our results suggest that this ncRNA-dependent mechanism evolved to survey the worm’s microbial environment, use this information to make appropriate behavioral decisions, and pass this information on to its progeny.

scholarly journals A Waddington Epigenetic Landscape for the C. elegans embryo

2020 ◽  
Author(s):  
Ahmed Elewa
Keyword(s):  
Stress Response ◽  
Embryonic Development ◽  
Small Rnas ◽  
Expression Profiles ◽  
Epigenetic Landscape ◽  
C Elegans ◽  
Visual Model ◽  
Similar Expression ◽  
Redundant Genes ◽  
And Behavior

AbstractWaddington’s Epigenetic Landscape provides a visual model for both robust and adaptable development. Generating and exploring a Waddington epigenetic landscape for the early C. elegans embryo suggests that the key shapers of the landscape are genes that lie at the nexus between stress response and behavior and include genes that are regulated by transgenerational neuronal small RNAs. Curiously, several genes shape the early landscape of one lineage and then pattern, differentiate or are enriched in another lineage. Additionally, paralogs with similar expression profiles contribute differently to shaping the modeled landscape. This work suggests that robust embryonic development is initialized by differential deployment of redundant genes and by transgenerational cues that configure the epigenetic landscape to adapt to a changing world.

scholarly journals QsRNA-seq: a method for high-throughput profiling and quantifying small RNAs

2018 ◽  
Author(s):  
Alla Fishman ◽  
Dean Light ◽  
Ayelet T. Lamm
Keyword(s):  
High Throughput ◽  
Small Rnas ◽  
High Throughput Sequencing ◽  
Developmental Stages ◽  
Biological Research ◽  
C Elegans ◽  
Cellular Processes ◽  
Repetitive Nature ◽  
Developmental Role ◽  
Non Coding Rnas

The finding that small non-coding RNAs (sRNAs) can affect cellular processes by regulating gene expression had a significant impact on biological research and clinical diagnosis. Yet, the ability to quantify and profile sRNAs, specifically miRNAs, using high-throughput sequencing is especially challenging because of their small size and repetitive nature. We developed QsRNA-seq, a method for preparation of sRNA libraries for high-throughput sequencing that overcomes this difficulty by enabling separation of fragments shorter than 100nt long that differ only by 20nt in length. The method supports using unique molecular identifiers for quantification. We show that QsRNA-seq gives very accurate, comprehensive and reproducible results. Using QsRNA-seq to study the miRNA repertoire in C. elegans embryo and L4 larval developmental stages, enabled extending the list of miRNAs that are expressed in a developmental-specific manner. Interestingly, we found that miRNAs 23nt long are predominantly expressed in developmental stage L4, suggesting a possible connection between the length of miRNA and its developmental role.

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