MicroRNA Destabilization Enables Dynamic Regulation of the miR-16 Family in Response to Cell-Cycle Changes

SummaryThe miR-16 family, which targets genes important for the G1-S transition, is a known modulator of the cell cycle, and members of this family are often deleted or downregulated in many types of cancers. Here, we report the reciprocal relationship—that of the cell cycle controlling the miR-16 family. Levels of this family increase rapidly as cells are arrested in G0. Conversely, as cells are released from G0 arrest, levels of the miR-16 family rapidly decrease. Such rapid changes are made possible by the unusual instabilities of several family members. The repression mediated by the miR-16 family is sensitive to these cell-cycle changes, which suggests that the rapid upregulation of the miR-16 family reinforces cell-cycle arrest in G0. Upon cell-cycle re-entry, the rapid decay of several members allows levels of the family to decrease, alleviating repression of target genes and allowing proper resumption of the cell cycle.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (63 K)Download as PowerPoint slideHighlights▸ The miR-16 family increases during cell-cycle exit and decreases during re-entry ▸ The changes in miRNA levels can change the amount of target repression ▸ The constitutive instability of the miRNAs facilitates their rapid decrease ▸ The determinants of miR-503 instability map to its 5′ and 3′ end regions