Polyamines have been discovered for hundreds of years and once considered as a class of phytohormones. Polyamines play critical roles in a range of developmental processes. However, the molecular mechanisms of polyamines signaling remain poorly understood. Here, we measured the contents of main types of polyamines and found that endogenous level of thermospermine (T-Spm) in Arabidopsis thaliana is comparable to those of classic phytohormones and is significantly lower than those of putrescine (Put), spermidine (Spd), and spermine (Spm). We further found a nodule-like structure around the junction area connecting the shoot and root of the T-Spm biosynthetic mutant acl5 and obtained more than 50 suppressors of acl5 nodule structure (san) through suppressor screening. An in-depth study of two san suppressors revealed that NAP57 and NOP56, core components of box H/ACA and C/D snoRNPs, were essential for T-Spm-mediated nodule-like structure formation and plant height. Furthermore, analyses of rRNA modifications showed that the overall levels of pseudouridylation and 2'-O-methylation were compromised in san1 and san2 respectively. Taken together, these results establish a strong genetic relationship between rRNA modification and T-Spm-mediated growth and development, which was previously undiscovered in all organisms.