{"doi":"10.1093/nar/gkaa717","title":"Ribosomal stalk proteins RPLP1 and RPLP2 promote biogenesis of flaviviral and cellular multi-pass transmembrane proteins","abstract":"The ribosomal stalk proteins, RPLP1 and RPLP2 (RPLP1/2), which form the ancient ribosomal stalk, were discovered decades ago but their functions remain mysterious. We had previously shown that RPLP1/2 are exquisitely required for replication of dengue virus (DENV) and other mosquito-borne flaviviruses. Here, we show that RPLP1/2 function to relieve ribosome pausing within the DENV envelope coding sequence, leading to enhanced protein stability. We evaluated viral and cellular translation in RPLP1/2-depleted cells using ribosome profiling and found that ribosomes pause in the sequence coding for the N-terminus of the envelope protein, immediately downstream of sequences encoding two adjacent transmembrane domains (TMDs). We also find that RPLP1/2 depletion impacts a ribosome density for a small subset of cellular mRNAs. Importantly, the polarity of ribosomes on mRNAs encoding multiple TMDs was disproportionately affected by RPLP1/2 knockdown, implying a role for RPLP1/2 in multi-pass transmembrane protein biogenesis. These analyses of viral and host RNAs converge to implicate RPLP1/2 as functionally important for ribosomes to elongate through ORFs encoding multiple TMDs. We suggest that the effect of RPLP1/2 at TMD associated pauses is mediated by improving the efficiency of co-translational folding and subsequent protein stability.","journal":"Nucleic Acids Research","year":2020,"id":63943,"datarank":1.212875998781539,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.6558401887758927,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.6558401887758927,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":33,"citers_with_citation_signal":25,"citers_with_endowment":25,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":337961,"name":"H. R. Sagara Wijeratne","orcid":"0000-0002-8209-5626","position":1,"is_corresponding":false},{"id":17872,"name":"Premal Shah","orcid":"0000-0002-8424-4218","position":2,"is_corresponding":false},{"id":232721,"name":"Mariano A. García-Blanco","orcid":"0000-0001-8538-1997","position":3,"is_corresponding":false},{"id":276957,"name":"Shelton S. Bradrick","orcid":"0000-0003-1566-9797","position":4,"is_corresponding":false},{"id":297457,"name":"Rafael K. Campos","orcid":"0000-0002-4852-0449","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:11:24.000992Z","pmid":"32890404","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":[]}