Mesorhizobium spp. are ubiquitous soil bacteria often capable of forming nitrogen-fixing symbioses with legume plants. Quorum sensing is a form of chemical cell-cell communication bacteria use to coordinate a variety of activities, often those which serve a public good in clonal populations or benefit from coordinated population-level expression. We bioinformatically identified a LuxR/LuxI-family N-acyl-homoserine lactone (AHL) quorum sensing system conserved in 206/214 unique sequenced Mesorhizobium spp., named here MQS. In addition to the regulator gene mqsR and AHL-synthase gene mqsI, the MQS locus includes a conserved mqsC gene encoding a putative crotonase-family protein. Mutational analysis and mass spectrometry revealed both MqsI and MqsC together synthesise the diunstaturated N-((2E,4E)-2,4-dodecadienoyl) homoserine lactone (abbreviated 2,4-trans-C12-HSL), making MQS the only known LuxRI-family quorum sensing system to encode two proteins for AHL-synthesis. MqsR-dependent promoters responded most highly to synthesised 2,4-trans-C12-HSL compared to other C12-HSL derivatives or short-chain AHLs, suggesting Mesorhizobium spp. utilise 2,4-trans-C12-HSL to communicate specifically with each other. RNA transcriptome sequencing of mqsRIC-mutants revealed very few changes in the abundance of protein-coding mRNAs but inspection of mapped RNA reads led to the identification of seven novel non-coding RNA genes scattered throughout the chromosome, mqsRNA1-mqsRNA7. Transcription of mqsRNA1-mqsRNA7 required mqsR and 2,4-trans-C12-HSL. Interestingly, the eight (of 214) Mesorhizobium spp. lacking the mqsRIC locus also lacked mqsRNA1-mqsRNA7. Promoter truncations and transcriptional fusions revealed MqsR directly activates transcription downstream of a “GYGATCRC” motif, likely representing the MqsR binding site. The small RNA chaperone Hfq was used to capture and sequence small RNA interactions with target mRNAs (termed Hfq-CLASH). These analyses reveal that the most abundant MqsR-activated non-coding RNA, mqsRNA7, tentatively binds the 5-untranslated regions of numerous mRNA transcripts coding for proteins involved in nutrient uptake and membrane transport.