Fibroblast growth factor 2 (FGF-2) is a novel substrate for arginine methylation by PRMT5

Abstract

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.