WormBase in 2022—data, processes, and tools for analyzing <i>Caenorhabditis elegans</i>

Davis, Paul A.; Zarowiecki, Magdalena; Arnaboldi, Valerio; Becerra, Andrés; Cain, Scott; Chan, Juancarlos; Chen, Wen J.; Cho, Jae Hyoung; Beltrame, Eduardo da Veiga; Diamantakis, Stavros; Gao, Sibyl; Grigoriadis, Dionysios; Grove, Christian A.; Harris, Todd W.; Kishore, Ranjana; Lê, Tuấn Anh; Lee, Raymond Y. N.; Luypaert, Manuel; Müller, Hans‐Michael; Nakamura, Cecilia; Nuin, Paulo; Paulini, Michael; Quinton-Tulloch, Mark; Raciti, Daniela; Rodgers, Faye H.; Russell, Matthew; Schindelman, Gary; Archana, Archana; Stickland, Tim; Auken, Kimberly Van; Wang, Qinghua; Williams, Gary W.; Wright, Adam; Yook, Karen; Berriman, Matt; Howe, Kevin; Schedl, Tim; Stein, Lincoln; Sternberg, Paul W.

doi:10.1093/genetics/iyac003

Cited by 208 publications

(190 citation statements)

References 50 publications

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“…0 of 72 progeny from it!s37 + I + puf-ll(tn1824) parents carried a recombinant it!s37 puf-ll(tn1824) chromosome, while 5 of 64 progeny from it!s37 + I + puf-3(tn1820) parents carried a recombinant it!s37 puf-3(tn1820) chromosome. Together, these observations suggested that it!s37 is ∼7.8 map units to the left of puf-3 , in good agreement with the relative genetic positions of puf-ll and puf-3 described in WormBase (http://www.wormbase.org, release WS278; Davis et al . 2022).…”

Section: Methodssupporting

confidence: 81%

Ubiquitin ligases and a processive proteasome facilitate protein clearance during the oocyte-to-embryo transition in Caenorhabditis elegans

Spike

Tsukamoto

Greenstein

2021

Preprint

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The ubiquitin-mediated degradation of oocyte translational regulatory proteins is a conserved feature of the oocyte-to-embryo transition (OET). In the nematode Caenorhabditis elegans, multiple translational regulatory proteins, including the TRIM-NHL RNA-binding protein LIN-41/Trim71 and the Pumilio-family RNA-binding proteins PUF-3 and PUF-11, are degraded during the OET. Degradation of each protein requires activation of the M-phase cyclin-dependent kinase CDK-1, is largely complete by the end of the first meiotic division and does not require the anaphase promoting complex (APC). However, only LIN-41 degradation requires the F-box protein SEL-10/FBW7/Cdc4p, the substrate recognition subunit of an SCF-type E3 ubiquitin ligase. This finding suggests that PUF-3 and PUF-11, which localize to LIN-41-containing ribonucleoprotein particles (RNPs), are independently degraded through the action of other factors and that the oocyte RNPs are disassembled in a concerted fashion during the OET. We develop and test the hypothesis that PUF-3 and PUF-11 are targeted for degradation by the proteasome-associated HECT-type ubiquitin ligase ETC-1/UBE3C/Hul5, which is broadly expressed in C. elegans. We find that several GFP-tagged fusion proteins that are degraded during the OET, including fusions with PUF-3, PUF-11, LIN-41, IFY-1/Securin and CYB-1/Cyclin B, are incompletely degraded when ETC-1 function is compromised. However, it is the fused GFP moiety that appears to be the critical determinant of this proteolysis defect. These findings are consistent with a conserved role for ETC-1 in promoting proteasome processivity and suggest that proteasomal processivity is an important element of the OET during which many key oocyte regulatory proteins are rapidly targeted for degradation.Article SummaryThe ubiquitin-mediated degradation of translational regulatory RNA-binding proteins is a conserved feature of the oocyte-to-embryo transition (OET). C. elegans LIN-41 is a master regulator of oogenesis and is found in a large translational regulatory ribonucleoprotein (RNP) complex with more than 1000 maternal transcripts and the Pumilio-family RNA-binding proteins PUF-3 and PUF-11. We show that the concerted action of ubiquitin-mediated protein degradation and proteasome processivity rapidly disassemble LIN-41-containing RNPs during the OET thereby relieving repression of many maternal transcripts.

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Section: Methodssupporting

confidence: 81%

Ubiquitin ligases and a processive proteasome facilitate protein clearance during the oocyte-to-embryo transition in Caenorhabditis elegans

Spike

Tsukamoto

Greenstein

2021

Preprint

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“…Whilst the absence of nape in some species may be explained by genome quality, in other species with robust genome data an alternative AEA synthesis pathway may exist (see below). Previous studies have demonstrated the presence of two, functionally divergent, nape orthologs in C. elegans that occupy adjacent genomic positions ( nape -1, IV:3739520..3740880 ; nape -2, IV:3735470..3738925; [WormBase; (Davis et al, 2022)], share 73% sequence identity, and display complete conservation of the NAPE-PLD signature sequence (Harrison et al, 2014). Our pan-phylum analysis confirms that C. elegans is the only nematode species that possesses two distinct NAPE-encoding genes.…”

Section: Resultsmentioning

confidence: 99%

Pan-phylum In Silico Analyses of Nematode Endocannabinoid Signalling Systems Highlight Novel Opportunities for Parasite Drug Target Discovery

Crooks

Mckenzie

Cadd

et al. 2022

Preprint

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The endocannabinoid signalling (ECS) system is a complex lipid signalling pathway that modulates diverse physiological processes in both vertebrate and invertebrate systems. In nematodes, knowledge of endocannabinoid (EC) biology is derived primarily from the free-living model species Caenorhabditis elegans, where ECS has been linked to key aspects of nematode biology. The conservation and complexity of nematode ECS beyond C. elegans is largely uncharacterised, undermining the understanding of ECS biology in nematodes including species with key importance to human, veterinary and plant health. In this study we exploited publicly available omics datasets, in silico bioinformatics and phylogenetic analyses to examine the presence, conservation and life-stage expression profiles of EC-effectors across phylum Nematoda. Our data demonstrate that: (i) ECS is broadly conserved across phylum Nematoda, including in therapeutically and agriculturally relevant species; (ii) EC-effectors appear to display clade and lifestyle-specific conservation patterns; (iii) filarial species possess a reduced EC-effector complement; (iv) there are key differences between nematode and vertebrate EC-effectors; (v) life stage-, tissue- and sex-specific EC-effector expression profiles suggest a role for ECS in therapeutically relevant parasitic nematodes. These data also highlight putative novel targets for anthelmintic therapies. To our knowledge, this study represents the most comprehensive characterisation of ECS pathways in phylum Nematoda and inform our understanding of nematode ECS complexity. Fundamental knowledge of nematode ECS systems will seed follow-on functional studies in key nematode parasites to underpin novel drug target discovery efforts.

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“…Expression pattern tissue (categorical) Wormbase (29) Expression pattern lifestage (categorical) Wormbase ( 29)…”

Section: Datafield Sourcementioning

confidence: 99%

Supervised machine learning with feature selection for prioritization of targets related to time-based cellular dysfunction in aging

Truter¹,

Rensburg²,

Oudrhiri

et al. 2022

Preprint

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Background: Global life expectancy has been increasing without a corresponding increase in health span and with greater risk for aging-associated diseases such as Alzheimer′s disease (AD). An urgent need to delay the onset of aging-associated diseases has arisen and a dramatic increase in the number of potential molecular targets has led to the challenge of prioritizing targets to promote successful aging. Here, we developed a pipeline to prioritize aging-related genes which integrates the plethora of publicly available genomic, transcriptomic, proteomic and morphological data of C. elegans by applying a supervised machine learning approach. Additionally, a unique biological post-processing analysis of the computational output was performed to better reveal the prioritized gene′s function within the context of pathways and processes involved in aging across the lifespan of C. elegans. Results: Four known aging-related genes, daf-2, involved in insulin signaling; let-363 and rsks-1, involved in mTOR signaling; age-1, involved in PI3 kinase signaling, were present in the top 10% of 4380 ranked genes related to different markers of cellular dysfunction, validating the computational output. Further, our ranked output showed that 91% of the top 438 ranked genes consisted of known genes on GenAge, while the remaining genes had thus far not yet been associated with aging-related processes. Conclusion: These ranked genes can be translated to known human orthologs potentially uncovering previously unknown information about the basic aging processes in humans. These genes (and their downstream pathways) could also serve as targets against aging-related diseases, such as AD.

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WormBase in 2022—data, processes, and tools for analyzing Caenorhabditis elegans

Cited by 208 publications

References 50 publications

Ubiquitin ligases and a processive proteasome facilitate protein clearance during the oocyte-to-embryo transition in Caenorhabditis elegans

Ubiquitin ligases and a processive proteasome facilitate protein clearance during the oocyte-to-embryo transition in Caenorhabditis elegans

Pan-phylum In Silico Analyses of Nematode Endocannabinoid Signalling Systems Highlight Novel Opportunities for Parasite Drug Target Discovery

Supervised machine learning with feature selection for prioritization of targets related to time-based cellular dysfunction in aging

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