Arginine methylation mediated by the Arabidopsis homolog of PRMT5 is essential for proper pre-mRNA splicing
- aState Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
- bGraduate School of the Chinese Academy of Sciences, Beijing 100039, China;
- cNortheast Forestry University, Harbin 150040, China;
- dBeijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China; and
- eCollege of Life Science and Technology, Shanxi University, Taiyuan 030006, China
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Edited by Caroline Dean, The John Innes Centre, Norwich, United Kingdom, and approved September 28, 2010 (received for review July 12, 2010)
↵1X.D., L.G., C.L., and T.L contributed equally to this work.

Abstract
Protein arginine methylation, one of the most abundant and important posttranslational modifications, is involved in a multitude of biological processes in eukaryotes, such as transcriptional regulation and RNA processing. Symmetric arginine dimethylation is required for snRNP biogenesis and is assumed to be essential for pre-mRNA splicing; however, except for in vitro evidence, whether it affects splicing in vivo remains elusive. Mutation in an Arabidopsis symmetric arginine dimethyltransferase, AtPRMT5, causes pleiotropic developmental defects, including late flowering, but the underlying molecular mechanism is largely unknown. Here we show that AtPRMT5 methylates a wide spectrum of substrates, including some RNA binding or processing factors and U snRNP AtSmD1, D3, and AtLSm4 proteins, which are involved in RNA metabolism. RNA-seq analyses reveal that AtPRMT5 deficiency causes splicing defects in hundreds of genes involved in multiple biological processes. The splicing defects are identified in transcripts of several RNA processing factors involved in regulating flowering time. In particular, splicing defects at the flowering regulator FLOWERING LOCUS KH DOMAIN (FLK) in atprmt5 mutants reduce its functional transcript and protein levels, resulting in the up-regulation of a flowering repressor FLOWERING LOCUS C (FLC) and consequently late flowering. Taken together, our findings uncover an essential role for arginine methylation in proper pre-mRNA splicing that impacts diverse developmental processes.
Footnotes
- 2To whom correspondence should be addressed. E-mail: xfcao{at}genetics.ac.cn.
Author contributions: X.D., C.L., F.L., and X.C. designed research; X.D., C.L., T.L., F.L., P.C., and Y.P. performed research; L.G., Z.L., B.W., and S.H. analyzed data; and X.D., C.L., and X.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The RNA sequencing dataset was deposited in the Gene Expression Omnibus database at NCBI (accession no. GSE21323).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1009669107/-/DCSupplemental.
Freely available online through the PNAS open access option.