{"doi":"10.3390/ijms26136318","title":"NsrR Represses σE-Dependent Small RNAs and Interacts with RpoE via a Noncanonical Mechanism in Escherichia coli","abstract":"The envelope stress response in Escherichia coli is primarily governed by the sigma factor RpoE (σE), which activates protective genes upon membrane perturbation. Under non-stress conditions, σE is sequestered by its anti-sigma factor RseA. In this study, we identify an unexpected role for the nitric-oxide-sensing repressor NsrR in dampening σE activity and repressing σE-dependent small RNAs, including rybB, micA, and micL. Overexpression of nsrR represses transcription from σE-dependent promoters and phenocopies σE inactivation, resulting in filamentous morphology and growth defects. Conversely, ΔnsrR de-represses σE targets, with additive effects in rseA mutants—supporting an RseA-independent regulatory role. Time-course analysis shows NsrR represses σE activity, with kinetics comparable to those of RseA. While in vitro assays failed to detect robust NsrR binding to σE target promoters, NsrR directly interacts with σE in bacterial two-hybrid assays. Structural modeling using AlphaFold3 supports a plausible NsrR–RpoE interaction interface. These findings suggest that NsrR functions as a noncanonical anti-sigma-like modulator of σE, integrating redox and envelope stress signals to maintain membrane homeostasis.","journal":"International Journal of Molecular Sciences","year":2025,"id":569476,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":795740,"name":"Jalisa Nurse","orcid":null,"position":1,"is_corresponding":false},{"id":1125371,"name":"Dale E. A. Lewis","orcid":"0009-0001-1119-8652","position":2,"is_corresponding":false},{"id":329472,"name":"Chin‐Hsien Tai","orcid":"0000-0003-4766-0535","position":3,"is_corresponding":false},{"id":795275,"name":"Karl M. Thompson","orcid":"0000-0001-6182-9507","position":4,"is_corresponding":false},{"id":795274,"name":"Joseph I Aubee","orcid":"0000-0003-2849-296X","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T02:56:59.652443Z","pmid":"40650095","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":[]}