{"doi":"10.1016/j.jbc.2025.110369","title":"Regulation of steady state ribosomal transcription in Mycobacterium tuberculosis: Intersection of sigma subunits, superhelicity, and transcription factors","abstract":"Ribosomal RNA (rRNA) regulation in Mycobacterium tuberculosis ( Mtb ) is tightly linked to nutrient availability, growth phase, and global gene expression, influencing Mtb's adaptability and pathogenicity. Unlike most bacteria, Mtb has a single ribosomal operon with two promoters, rrnA P3 and rrnA P1, and a high ratio of sigma (σ) factors to genome size. While σ A is the primary driver of ribosomal transcription, σ B has been suggested to contribute under various conditions, though its role remains unclear. Here, we quantify steady-state transcription rates in reconstituted reactions and demonstrate that σ A -driven transcription from rrnA P3 dominates rRNA production, with minimal contributions from σ B or rrnA P1. Kinetic analysis suggests that σ B holoenzymes exhibit slower DNA unwinding and holoenzyme recycling. We also show that transcription factors CarD and RbpA reverse and buffer, respectively, the stimulatory effects of negative superhelicity on σ A -driven rRNA transcription. Finally, we identify the N-terminal 205 amino acids of σ A as a key determinant of its increased activity relative to σ B . Our findings reveal the intricate interplay of promoter sequence, σ factor identity, DNA superhelicity, and transcription factors in shaping transcription initiation kinetics to ultimately influence rRNA production in Mtb .","journal":"Journal of Biological Chemistry","year":2025,"id":521404,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"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":833080,"name":"Drake Jensen","orcid":"0000-0002-4227-8241","position":1,"is_corresponding":false},{"id":731109,"name":"Eric A. Galburt","orcid":"0000-0003-4314-3215","position":2,"is_corresponding":false},{"id":833081,"name":"Ana Ruiz Manzano","orcid":"0000-0001-9135-1436","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":null,"created_at":"2026-07-19T02:49:44.558743Z","pmid":"40516872","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":[]}