{"doi":"10.1101/2023.02.07.527351","title":"Target-specific requirements for RNA interference can arise through restricted RNA amplification despite the lack of specialized pathways","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  Since double-stranded RNA (dsRNA) is effective for silencing a wide variety of genes, all genes are typically considered equivalent targets for such RNA interference (RNAi). Yet, loss of some regulators of RNAi in the nematode\n                  <jats:italic>C. elegans</jats:italic>\n                  can selectively impair the silencing of some genes. Here we show that such selective requirements can be explained by an intersecting network of regulators acting on genes with differences in their RNA metabolism. In this network, the Maelstrom domain-containing protein RDE-10, the intrinsically disordered protein MUT-16, and the Argonaute protein NRDE-3 work together so that any two are required for silencing one somatic gene, but each is singly required for silencing another somatic gene, where only the requirement for NRDE-3 can be overcome by enhanced dsRNA processing. Quantitative models and their exploratory simulations led us to find that (1) changing\n                  <jats:italic>cis</jats:italic>\n                  -regulatory elements of the target gene can reduce the dependence on NRDE-3, (2) animals can recover from silencing in non-dividing cells and (3) cleavage and tailing of mRNAs with UG dinucleotides, which makes them templates for amplifying small RNAs, is enriched within ‘pUG zones’ matching the dsRNA. Similar crosstalk between pathways and restricted amplification could result in apparently selective silencing by endogenous RNAs.\n                </jats:p>","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":null,"id":35462,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":181564,"name":"Pravrutha Raman","orcid":"0000-0002-7435-9425","position":1,"is_corresponding":false},{"id":181565,"name":"Farida Ettefa","orcid":"0000-0003-0433-5951","position":2,"is_corresponding":false},{"id":181566,"name":"Laura De Ravin","orcid":null,"position":3,"is_corresponding":false},{"id":181567,"name":"Antony M. Jose","orcid":"0000-0003-1405-0618","position":4,"is_corresponding":false},{"id":181563,"name":"Daphne R. Knudsen-Palmer","orcid":"0000-0001-5745-1185","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36798330","pmcid":null,"openalex_id":"https://openalex.org/W4319592712","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"1R01GM124356-01A1","title":"Transgenerational gene silencing by extracellular RNA"},{"funder_name":"National Science Foundation","grant_id":"2120895","title":"MCA: Quantitative understanding of heritable epigenetic changes"},{"funder_name":"National Institutes of Health","grant_id":"1R01GM111457-01","title":"Movement of RNA between animal cells"},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM111457","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM124356","title":null}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2023,"count":1},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2023/02/08/2023.02.07.527351.full.pdf","host_type":"repository"},{"url":"https://doi.org/10.7554/elife.97487","host_type":"GREEN"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2023/02/08/2023.02.07.527351.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2023.02.07.527351","host_type":"publisher"},{"url":"https://doi.org/10.1101/2023.02.07.527351","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36798330","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9934570","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9934570/pdf/nihpp-2023.02.07.527351v3.pdf","host_type":"repository"},{"url":"https://doi.org/10.7554/elife.97487.2","host_type":""},{"url":"https://doi.org/10.7554/elife.97487.1","host_type":""},{"url":"https://doi.org/10.7554/elife.97487.3","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/39161220","host_type":""},{"url":"http://dx.doi.org/10.1101/2023.02.07.527351","host_type":""},{"url":"http://dx.doi.org/10.7554/eLife.97487","host_type":""},{"url":"https://doaj.org/article/cf317cf7db4344019722101c3d74a67c","host_type":""}],"fields_of_study":["CRISPR and Genetic Engineering","RNA regulation and disease","Genetics, Aging, and Longevity in Model Organisms","Medicine","Biology","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Argonaute","RNA silencing","RNA interference","Gene silencing","Biology","RNA-induced silencing complex","Trans-acting siRNA","RNA","Piwi-interacting RNA","Gene","RasiRNA","Genetics","RNA-induced transcriptional silencing","Cell biology","DNA-directed RNA interference","Computational biology","epigenetics","QH301-705.5","Science","Q","R","RNA-Binding Proteins","Chromosomes and Gene Expression","pUG RNA","Article","Medicine","Animals","regulation of gene expression","Biology (General)","Caenorhabditis elegans","Caenorhabditis elegans Proteins","RNA, Double-Stranded"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T04:04:44.692957Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}