Recruitment of the NineTeen Complex to the activated spliceosome requires AtPRMT5.
Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is involved in a multitude of biological processes in eukaryotes. Symmetric arginine dimethylation mediated by PRMT5 modulates constitutive and alternative pre-mRNA splicing of diverse genes to regulate normal growth and development in multiple species; however, the underlying molecular mechanism remains largely unknown. A genetic screen for suppressors of an Arabidopsis symmetric arginine dimethyltransferase mutant, atprmt5, identified two gain-of-function alleles of pre-mRNA processing factor 8 gene (prp8-8 and prp8-9), the highly conserved core component of the U5 small nuclear ribonucleoprotein (snRNP) and the spliceosome. These two atprmt5 prp8 double mutants showed suppression of the developmental and splicing alterations of atprmt5 mutants. In atprmt5 mutants, the NineTeen complex failed to be assembled into the U5 snRNP to form an activated spliceosome; this phenotype was restored in the atprmt5 prp8-8 double mutants. We also found that loss of symmetric arginine dimethylation of Sm proteins prevents recruitment of the NineTeen complex and initiation of spliceosome activation. Together, our findings demonstrate that symmetric arginine dimethylation has important functions in spliceosome assembly and activation, and uncover a key molecular mechanism for arginine methylation in pre-mRNA splicing that impacts diverse developmental processes.
State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, CAS Center for Excellence in Molecular Plant Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
Xian
X
Deng
State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, CAS Center for Excellence in Molecular Plant Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
Tiancong
T
Lu
State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, CAS Center for Excellence in Molecular Plant Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
Lulu
L
Wang
State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, CAS Center for Excellence in Molecular Plant Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
Lianfeng
L
Gu
State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, CAS Center for Excellence in Molecular Plant Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
Jing
J
Sun
State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, CAS Center for Excellence in Molecular Plant Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
Xiangfeng
X
Kong
State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, CAS Center for Excellence in Molecular Plant Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; cyliu@genetics.ac.cn xfcao@genetics.ac.cn.
Chunyan
C
Liu
State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, CAS Center for Excellence in Molecular Plant Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai 200438, China cyliu@genetics.ac.cn xfcao@genetics.ac.cn.
Xiaofeng
X
Cao
D017360:Arabidopsis / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D017381:Spliceosomes / Q000235:genetics*
D029681:Arabidopsis Proteins; D012322:RNA Precursors; D029701:Saccharomyces cerevisiae Proteins; C507652:Spp382 protein, S cerevisiae; C524490:PRMT5 protein, Arabidopsis; D011484:Protein-Arginine N-Methyltransferases
AtPRMT5; Prp19C/NTC; arginine methylation; pre-mRNA splicing; protein arginine methyltransferase