Role of PRMTs in cancer: Could minor isoforms be leaving a mark?

Abstract

Protein arginine methyltransferases (PRMTs) catalyze the methylation of a variety of protein substrates, many of which have been linked to the development, progression and aggressiveness of different types of cancer. Moreover, aberrant expression of PRMTs has been observed in several cancer types. While the link between PRMTs and cancer is a relatively new area of interest, the functional implications documented thus far warrant further investigations into its therapeutic potential. However, the expression of these enzymes and the regulation of their activity in cancer are still significantly understudied. Currently there are nine main members of the PRMT family. Further, the existence of alternatively spliced isoforms for several of these family members provides an additional layer of complexity. Specifically, PRMT1, PRMT2, CARM1 and PRMT7 have been shown to have alternative isoforms and others may be currently unrealized. Our knowledge with respect to the relative expression and the specific functions of these isoforms is largely lacking and needs attention. Here we present a review of the current knowledge of the known alternative PRMT isoforms and provide a rationale for how they may impact on cancer and represent potentially useful targets for the development of novel therapeutic strategies.

Keywords: Protein arginine methyltransferase, Arginine methylation, Cancer, Alternative splicing, Isoforms

Core tip: This review focuses on the current knowledge regarding alternative protein arginine methyltransferases (PRMT) isoforms and evidence supporting their potential impact in cancer. Alternative PRMT isoforms have been identified for PRMT1, PRMT2, CARM1 and PRMT7 and more may exist for the other PRMT family members. The presence of these isoforms adds a layer of complexity to the functional roles PRMTs play in normal and disease contexts. These alternative isoforms have unique characteristics that may offer clarification to conflicting roles documented in the literature. Finally, understanding the specific functions of these isoforms is crucial for fully characterizing the therapeutic potential of PRMTs in cancer.