Fibroblast growth factor 2 (FGF-2) is a novel substrate for arginine methylation by PRMT5.
Fibroblast growth factor 2 (FGF-2) is expressed in isoforms of different molecular masses from one mRNA species by alternative start of translation. The higher molecular mass isoforms (FGF-2(21) and (23)) contain an arginine-rich N-terminus organized in RG-motifs followed by the 18 kDa FGF-2 (FGF-2(18)) core which is common to all isoforms. Both isoforms localize differentially to the nucleus. Here, we analyzed the nuclear localization of FGF-2(21). Surprisingly, the lack of one RG-motif in FGF-2(21) resulted in the nucleolar distribution characteristic of FGF-2(18). We have previously shown that 23 kDa FGF-2 (FGF-2(23)) interacts specifically with the survival of motoneuron (SMN) protein, an assembly protein for small nuclear ribonucleoprotein particles. For this assembly, Sm-proteins methylated by protein arginine methyltransferase 5 (PRMT5) are required. In our study, we aimed to analyze whether FGF-2(23) is also a substrate for symmetrical methylation by PRMT5. We could confirm that both proteins exist in a common complex. Moreover, PRMT5 methylates FGF-2(23) in vitro, whereas mutated inactive PRMT5 does not. FGF-2(23) is therefore a new substrate of PRMT5. With regard to function, inhibition of methyltransferase activity in HEK293T cells leads to cytoplasmic enrichment of FGF-2, indicating the importance of arginine methylation for shuttling of FGF-2(23) to the nucleus.
Bruns
Alexander-Francisco
AF
Hannover Medical School, Institute of Neuroanatomy, OE 4140, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Grothe
Claudia
C
Claus
Peter
P
D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D009154:Mutation; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016222:Fibroblast Growth Factor 2; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases