Heterogeneous nuclear ribonucleoprotein E1B-AP5 is methylated in its Arg-Gly-Gly (RGG) box and interacts with human arginine methyltransferase HRMT1L1

The heterogeneous nuclear ribonucleoprotein (hnRNP) family includes predomi nantly nuclear proteins acting at different stages of mRNA metabolism. A ch aracteristic feature of hnRNPs is to undergo post-translational asymmetric arginine methylation catalysed by different type 1 protein arginine methylt ransferases (PRMTs). A novel mammalian hnRNP, E1B-AP5, recently identified by its interaction with adenovirus early protein E1B-55 kDa, has been propo sed to have a regulatory role in adenoviral and host-cell mRNA processing/n uclear export [Gabler, Schutt, Groid, Wolf, Shenk and Dobner (1998) J. Viro l. 72, 7960-7971]. Here we report that E1B-AP5 is methylated in vivo in its Arg-Gly-Gly (RGG)-box domain, known to mediate protein-RNA interactions. T he activity responsible for E1B-AP5 methylation forms a complex with E1B-AP 5 in vivo. The predominant mammalian arginine methyltransferase HRM1L2 (hPR MT1) did not detectably methylate endogenous E1B-AP5 despite efficiently me thylating a recombinant RGG-box domain of E1B-AP5. Using yeast two-hybrid s creening we identified HRMT1L1 (PRMT2) as one of the proteins interacting w ith E1B-AP5. By in situ immunofluorescence we demonstrated that E1B-AP5 co- localizes with the nuclear fraction of HRMT1L1. The Src homology 3 (SH3) do main of HRMT1L1 was essential for its interaction with E1B-AP5 in vivo. We suggest that HRMT1L1 is responsible for specific E1B-AP5 methylation in viv o.