Recessive epistasis of a synonymous mutation confers cucumber domestication through epitranscriptomic regulation

This is the authors' abstract. We don't add key points for this paper.

Synonymous mutations, once known as "silent" mutations, are increasingly attracting the interest of biologists. Although they may affect transcriptional or post-transcriptional processes, their impact on biological traits remains under-investigated, particularly at the organismal level. Here, we identified two closely linked, epistatically interacting genes: YTH1 , an RNA N 6 -methyladenosine (m 6 A) reader, and ACS2 , an aminocyclopropane-1-carboxylic acid (ACC) synthase, which contribute to cucumber fruit length domestication. The causative mutation in ACS2 is a synonymous substitution at 1287C>T. In wild cucumber, ACS2 1287C results in m 6 A modification on nearby adenosine residues and the formation of loose RNA structural conformations. YTH1 recognizes the m 6 A modification, alters the folding equilibrium toward the weakest RNA structural conformation, and increases the ACS2 protein level, resulting in shorter fruit. In cultivated cucumber, ACS2 1287T disrupts m 6 A methylation and forms compact RNA structural conformations, leading to attenuated protein production and fruit elongation. This study provides genetic evidence of synonymous variation shaping a biological trait through epitranscriptomic regulations.