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We investigated the impact of temperature on the effects of six mutations on sequence, structure, transcriptome, and organismal traits. We found temperature altered the transcriptomic response and key organismal traits such as growth rate and biofilm formation in a genotype-specific manner. Critically, mechanistic insights into the possible drivers of mutational effects emerged only when examining the relationships between different levels of organization: location of mutations in the tertiary structure and distance to key interacting molecules partly explained the observed transcriptomic differences, which in turn drove the impact of mutations on organismal traits. While falling short of capturing the full complexity of the system, our findings underscore the benefits of integrating insights across multiple biological levels to understand the relationship between environment and mutational effects in molecules with extensive pleiotropic effects.<\/jats:p>","DOI":"10.1093\/molbev\/msaf226","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T22:25:54Z","timestamp":1758320754000},"source":"Crossref","is-referenced-by-count":1,"title":["Deciphering the Impact of Temperature on Pleiotropic Consequences of RNA Polymerase Mutations"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-7733","authenticated-orcid":false,"given":"Deniz","family":"Ozbilek","sequence":"first","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester , Manchester M13 9PL 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