Identification and functional characterization of novel murine DIS3L2 isoforms

RNases are key factors for the posttranscriptional control of gene expression due to their involvement in processing, degradation and quality control of all classes of RNA in eukaryotes. DIS3L2 is an evolutionarily conserved exoribonuclease involved in cytoplasmic RNA degradation pathways that regulate gene expression. Macrophages undergo great change in gene expression of specific genes that allow these cells to perform multiple functions in addition to defense against infection. Here, we analyzed the change in expression of macrophages genes in response to Leishmania major infection, and show evidence that the levels of RNases such as the RNA exosome, XRN1, and DIS3L2, are modulated by the infection. We then identified three DIS3L2 variants that are differentially expressed in murine macrophages and other cell lines. DIS3L2 isoforms show similar RNA binding affinity, but differences in exonucleolytic activity in in vitro assays. Furthermore, we characterized the interactome of the DIS3L2 variants, which shows similarities with respect to ribosomal proteins, but differences that hint at specific functions for each isoform. This work uncovers previously uncharacterized DIS3L2 isoforms that are active, whose functions have yet to be identified.