The methanol-derived methanogenetic pathway contributes to bulk methane production in cold regions, but the cold adaptation mechanisms are obscure. This work investigated the mechanisms using a psychrophilic methylotrophic methanogen Methanolobus psychrophilus R15. R15 possesses two mtaCB operon paralogues-encoding methanol:corrinoid methyltransferase that is key to methanol-based methanogenesis. Molecular combined methanogenic assays determined that MtaC1 is important in methanogenesis at the optimal temperature of 18 C, but MtaC2 can be a cold-adaptive paralogue by highly upregulated at 8 C. The 5 0 P-seq and 5 0 RACE all assayed that processing occurred at the 5 0 untranslated region (5 0 -UTR) of mtaC2; reporter genes detected higher protein expression, and RNA half-life experiments assayed prolonged lifespan of the processed transcript. Therefore, mtaC2 5 0 -UTR processing to move the bulged structure elevated both the translation efficiency and transcript stability. 5 0 P-seq, quantitative RT-PCR and northern blot all identified enhanced mtaC2 5 0 -UTR processing at 8 C, which could contribute to the upregulation of mtaC2 at cold. The R15 cell extract contains an endoribonuclease cleaving an identified 10 nt-processing motif and the native mtaC2 5 0 -UTR particularly folded at 8 C. Therefore, this study revealed a 5 0 -UTR processing mediated post-transcriptional regulation mechanism controlling the cold-adaptive methanolsupported methanogenetic pathway, which may be used by other methylotrophic methanogens.