MicroRNAs (miRNAs) typically regulate gene expression by binding to the 3' UTR of target mRNAs, leading to mRNA destabilization and translational repression. This study reveals that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts. Specifically, miR-671 directs Ago2-mediated cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus, resulting in decreased CDR1 mRNA levels. The study provides the first evidence that non-coding antisense transcripts can act as direct miRNA targets and suggests a novel regulatory mechanism involving a positive correlation between mRNA and circular antisense RNA levels. The CDR1 antisense transcript is circularized through non-linear splicing, forming a stable RNA that may regulate CDR1 mRNA levels. miR-671-mediated cleavage of the circular antisense transcript leads to its degradation and subsequent destabilization of CDR1 mRNA. The study also shows that miR-671-directed cleavage is Ago2-slicer-dependent and that the circular CDR1 antisense transcript is highly expressed in brain tissue. The findings highlight a novel miRNA-mediated regulatory mechanism involving non-coding antisense transcripts and suggest that miRNAs may have diverse biological functions beyond their canonical role in 3' UTR target mRNA repression.MicroRNAs (miRNAs) typically regulate gene expression by binding to the 3' UTR of target mRNAs, leading to mRNA destabilization and translational repression. This study reveals that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts. Specifically, miR-671 directs Ago2-mediated cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus, resulting in decreased CDR1 mRNA levels. The study provides the first evidence that non-coding antisense transcripts can act as direct miRNA targets and suggests a novel regulatory mechanism involving a positive correlation between mRNA and circular antisense RNA levels. The CDR1 antisense transcript is circularized through non-linear splicing, forming a stable RNA that may regulate CDR1 mRNA levels. miR-671-mediated cleavage of the circular antisense transcript leads to its degradation and subsequent destabilization of CDR1 mRNA. The study also shows that miR-671-directed cleavage is Ago2-slicer-dependent and that the circular CDR1 antisense transcript is highly expressed in brain tissue. The findings highlight a novel miRNA-mediated regulatory mechanism involving non-coding antisense transcripts and suggest that miRNAs may have diverse biological functions beyond their canonical role in 3' UTR target mRNA repression.