{"doi":"10.1101/2022.09.28.509886","title":"Hypodermal ribosome synthesis inhibition induces a nutrition-uncoupled organism-wide growth quiescence in <i>C. elegans</i>","abstract":"ABSTRACT Inter-organ communication is a key aspect of multicellular organismal growth, development, and homeostasis. Importantly, cell-non-autonomous inhibitory cues that limit tissue specific growth alterations are poorly characterized due to limitations of cell ablation approaches. Here, we report a robust system to investigate nutrition-independent organism-wide growth coordination by modulating ribosome biogenesis at distinct steps in a tissue-specific and reversible fashion in Caenorhabditis elegans . We find an organism-wide growth quiescence response upon suppression of ribosome synthesis either by depletion of an RNA polymerase I (Pol I) subunit or either of two critical ribosome biogenesis factors, RRB-1 and TSR-2, which are the chaperone proteins required for assembly of ribosomal proteins, RPL-3 and RPS-26, respectively. The observed organism-wide growth checkpoint is independent of the nutrition-dependent insulin signaling pathways and is not rescued by daf-16(mu86) , a bypass mutation that suppresses the starvation-induced quiescence response. Upon systematically exploring tissues involved in this process, we find that inhibition of hypodermal ribosome synthesis is sufficient to trigger an organism-wide growth quiescence response and leads to organism-wide gene expression changes. At the RNA level, we observe over- and under-expression of several tissue-restricted genes in a wide range of cell types, including touch receptor neurons suggesting inter-organ communication upon hypodermis driven ribosome inhibition. At the protein level, we observed over-expression of secreted proteins (CPR-4, TTR family proteins) as well as an organism-wide reduction both in cytosolic and mitochondrial ribosomal proteins in response to hypodermis RNA Pol I depletion. Finally, we find that dense core vesicle secretion specifically from the hypodermis tissue by the unc-31 gene plays a significant role in mediating the quiescence phenotype. Taken together, these results suggest the presence of a nutrition-independent multicellular growth coordination initiated from the hypodermis tissue.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301954,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":993479,"name":"Rekha Rangan","orcid":"0000-0001-5161-6655","position":1,"is_corresponding":false},{"id":993480,"name":"Shinuo Weng","orcid":"0000-0001-7932-913X","position":2,"is_corresponding":false},{"id":993984,"name":"Cem Özdemir","orcid":null,"position":3,"is_corresponding":false},{"id":554327,"name":"Elif Sarinay Cenik","orcid":"0000-0001-8514-5505","position":4,"is_corresponding":false},{"id":993478,"name":"Qiuxia Zhao","orcid":"0000-0001-9981-268X","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","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":[]}