NUDT21 Shapes Macrophage Transcriptomes through alternative polyadenylation in ARDS

Defining the molecular mechanisms governing macrophage-driven inflammation is essential for developing targeted interventions for ARDS. One such mechanism could be alternative polyadenylation (APA), a post-transcriptional regulatory process that plays a critical role in gene regulation. Most mammalian genes, including key proinflammatory mediators, contain multiple polyadenylation sites (PAS). APA regulates the addition of poly(A) tails at alternative PAS, generating transcripts with different 3' UTR lengths. One key regulator of APA is Nudix Hydrolase 21 (NUDT21), a critical cleavage factor Im (CFIm) component. However, whether NUDT21-mediated APA plays a role in inflammation during ARDS is not known. Thus, the goal of this study is to identify the APA genes regulated by NUDT21 in macrophages. Comparative analysis of alternative polyadenylation using polyA-click seq (PAC-seq) on Bone marrow derived macrophages collected from mice with myeloid NUDT21 deletion (NUDT21 f/f LysmCre) mice or control LysmCre mice treated with/without 1 ug/ml LPS for 3 hrs.