An mRNA silencing mechanism reliant on the cooperation between REGE-1/Regnase-1 and RLE-1/Roquin-1

Abstract

ABSTRACTRegnase-1 is an evolutionarily conserved endoribonuclease, degrading diverse mRNAs important, among others, for immune homeostasis, development, and cancer. There are two competing models of Regnase-1 mediated mRNA silencing. One model postulates that Regnase-1 works together with another RNA-binding protein, Roquin-1. The other model proposes that the two proteins function separately. Studying the C. elegans Regnase-1 ortholog, REGE-1, we have uncovered a functional relationship between REGE-1 and the nematode counterpart of Roquin-1, RLE-1. While REGE-1 and RLE-1 associate with mRNA independently of each other, both proteins are essential for mRNA silencing. Intriguingly, the functional interdependence between REGE-1 and RLE-1 is reminiscent of the proposed cooperation between mammalian Regnase-1 and Roquin-1, which may underlie a prototypic silencing mechanism involving both proteins.