Post-translational modification is the key step for regulating the biological functions of proteins. As an evolutionarily conserved post-translational modification, protein arginine methylation is involved in a multitude of biological processes in eukaryotes. It is catalyzed by protein arginine methyltransferases (PRMTs). Loss-of-function of PRMTs not only leads to developmental defects in mammals, but also results in genetic diseases and cancers in human beings.

AtPRMT5 is an essential protein arginine methyltransferase in Arabidopsis, which mediates the symmetric arginine dimethylation of histones and non-histone proteins. Loss-of-function of AtPRMT5 leads to multiple defects in plant development and pre-mRNA splicing of diverse genes as well. However, the underlying molecular mechanism remains largely unknown.

Researchers from Dr. CAO Xiaofeng’s group at the Institute of Genetics and Developmental Biology of Chinese Academy of Sciences elucidated the key molecular mechanism of AtPRMT5's role in pre-mRNA splicing. From a genetic screen, they identified two suppressors of atprmt5 mutants encoded by a highly conserved core component of the U5 small nuclear ribonucleoprotein (snRNP), Pre-mRNA Processing factor 8 (Prp8). These two suppressors showed suppression of the developmental and splicing alterations of atprmt5 mutants.

Proteomic analysis showed that the NineTeen complex failed to be assembled into the U5 snRNP to form an activated spliceosome, which was restored in the suppressors. Furthermore, the symmetric arginine dimethylation of Sm proteins was found to promote recruitment of the NineTeen complex and initiation of spliceosome activation, suggesting the key roles of symmetric arginine dimethylation in spliceosome assembly and activation.

This study elucidates a key molecular mechanism for arginine methylation in pre-mRNA splicing and in diverse developmental processes. It benefits the molecular mechanism of protein arginine methylation in plant development and the post-transcriptional evidence and clues for human genetic diseases and cancer research.

This work entitled “Recruitment of the NineTeen Complex to the activated spliceosome requires AtPRMT5” has been published online in PNAS.

This research was supported by the National Natural Science Foundation of China, the National Basic Research Program of China, and the State Key Laboratory of Plant Genomics.