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A functional antagonism between let-7 and miR-17 family members relying on sequences outside the seed

ABSTRACT: The canonical function of miRNAs relies on their ability to recognize and target messenger RNAs (mRNAs) through a mechanism known as seed pairing. The seed is a conserved sequence located at the 5'-end of the miRNA, and its specific pairing with the target mRNA is essential for target regulation. Surprisingly, we observed that miR-106a can bind to targets in place of let-7a despite the entirely different seed sequences. This binding does not depend on the seed sequence of miR-106a but instead relies on the extensive pairing on its 3'-end that shows homology with the let-7a seed sequence. miR-106a binding does not induce direct regulation of the bound targets. It shields them from seed-mediated pairing with let-7 family members, leading to competition for pairing with the same sequence in the target mRNA and resulting in two opposing functional outcomes: target repression by let-7a or target shielding by miR-106a. We conclude that by preventing let -7a from repressing oncogenic targets, the noncanonical binding of miR-106a contributes to cancer development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303559 | GEO | 2026/08/14

REPOSITORIES: GEO

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