Mouse anti-Human NUDT21 monoclonal antibody, clone 4G9

Widespread mRNA 3' UTR shortening through alternative polyadenylation(1) promotes tumor growth in vivo(2). A prevailing hypothesis is that it induces proto-oncogene expression in cis through escaping microRNA-mediated repression. Here we report a surprising enrichment of 3' UTR shortening among transcripts that are predicted to act as competingendogenous RNAs (ceRNAs) for tumor-suppressor genes. Our model-based analysis of the trans effect of 3' UTR shortening (MAT3UTR) reveals a significant role in altering ceRNA expression. MAT3UTR predicts many trans-targets of 3' UTR shortening, including PTEN, a crucial tumor-suppressor gene(3) involved in ceRNA crosstalk(4) with nine 3' UTRshortening genes, including EPS15 and NFIA. Knockdown of NUDT21, a master 3' UTR-shortening regulator(2), represses tumor-suppressor genes such as PHF6 and LARP1 in trans in a miRNA-dependent manner. Together, the results of our analysis suggest a major role of 3' UTR shortening in repressing tumor-suppressor genes in trans by disrupting ceRNA crosstalk, rather than inducing proto-oncogenes in cis.

Interstitial deletions of 16q chromosome including 16q12.1q21 region are very rare, with only three cases reported to date. Main clinical features include dysmorphisms, short stature, microcephaly, eye abnormalities, epilepsy, development delay, intellectual disability, and autism spectrum disorder. We report two independent subjects with 16q12.1q21 deletion syndrome presenting with dysmorphic facial features, developmental delay, strabismus, and aggressive behavior. A minimal region of overlap spanning 1.7 Mb on chromosome 16, including IRX5, GNAO1, and NUDT21 genes was shared among these two cases and those previously reported. This minimal region of overlap suggests the potential pathogenic role of these genes, previously implicated in diseases of the central nervous system.