GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318676/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318676GEOGSEfalsemRNA 3ʹ UTRs direct microRNA degradation to participate in imprinted gene networks and regulate growth dataset 5MicroRNAs direct downregulation of target mRNAs. Sometimes, however, this regulatory paradigm inverts, and a target RNA triggers degradation of a microRNA. This target-directed microRNA degradation (TDMD) requires ZSWIM8. Zswim8-/- mice exhibit reduced growth and perinatal lethality, accompanied by stabilization of >40 microRNAs. Nonetheless, studies of TDMD function in mammals have been limited because only two TDMD-triggering RNAs have been identified in mice. Here, we computationally identify and validate five new TDMD-triggering sites in mouse models. One site in Atp6v1g1 and two in Lpar4 direct degradation of miR-335-3p, showing that in mammals, two sites in the same transcript, and multiple sites in different transcripts, can collaborate to destabilize a microRNA. Moreover, sites in Plagl1 and Lrrc58 direct degradation of miR-322 and miR-503, respectively. Mice lacking the Plagl1 and Lrrc58 sites were smaller, demonstrating that target-directed degradation of miR-322 and miR-503 promotes growth. Both miR-335-3p and Plagl1 are maternally imprinted, implying their participation in parental conflict, but their corresponding triggers or target microRNA partner are not imprinted. Thus, 3¢ UTRs can participate in parental conflict not only by regulating protein production but also directly by engaging TDMD to access an additional layer of regulation within a network of imprinted and biallelic genes.2026/04/08GSE318676GSM9500433GSM9500444GSM9500443GSM9500432GSM9500442GSM9500431GSM9500441GSM9500430GSM9500452GSM9500451GSM9500440GSM9500450GSM9500429GSM9500439GSM9500438GSM9500449GSM9500448GSM9500437GSM9500436GSM9500447GSM9500446GSM9500435GSM9500445GSM950043424247318676Mus musculus[41871909]