{"doi":"10.1101/2021.03.29.437276","title":"Critical contribution of 3’ non-seed base pairing to the <i>in vivo</i> function of the evolutionarily conserved <i>let-7a</i> microRNA","abstract":"Summary Base-pairing of the seed region (g2-g8) is essential for microRNA targeting, however, the in vivo function of the 3’ non-seed region (g9-g22) are less well understood. Here we report the first systematic investigation of the in vivo roles of 3’ non-seed nucleotides in microRNA let-7a, whose entire g9-g22 region is conserved among bilaterians. We found that the 3’ non-seed sequence functionally distinguishes let-7a from its family paralogs. The complete pairing of g11-g16 is essential for let-7a to fully repress multiple key targets, including evolutionarily conserved lin-41 , daf-12 and hbl-1 . Nucleotides at g17-g22 are less critical but may compensate for mismatches in the g11-g16 region. Interestingly, the 3’ non-seed pairing of let-7a can be critically required with certain minimal complementarity for sites with perfect seed pairing. These results provide evidence that the specific configurations of both seed and 3’ non-seed base-pairing can critically influence microRNA-mediated gene regulation in vivo .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":217303,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":698445,"name":"Isana Veksler‐Lublinsky","orcid":"0000-0002-4251-6158","position":1,"is_corresponding":false},{"id":367672,"name":"Victor Ambros","orcid":"0000-0002-5562-5345","position":2,"is_corresponding":false},{"id":814117,"name":"Ye Duan","orcid":"0000-0003-2616-9368","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-18T23:53:20.374789Z","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":[]}