Although the recruitment of miRNA-induced silencing complex (miRISC) by miRNAs to the targeted mRNAs to regulate post-transcriptional gene expression is well documented, the mechanisms by which miRISC components are maintained at appropriate levels for proper function remain largely unknown. Here, we report the C. elegans TEG-1 (Tumorous Enhancer of
glp-1(gf)) regulates the stability of two miRISC effectors, VIG-1 and ALG-1, which in turn affects the abundance of various miRNA families. Loss of
teg-1 in vivo results in heterochronic defects, including excessive seam cell division and defective seam cell fusion. Since temporal developmental events are often controlled by miRNAs in C. elegans, we sought to determine if TEG-1 plays a role in miRNA function by identifying TEG-1-assoicated proteins. We found that TEG-1 physically interacts with VIG-1, and complexes with mature
let-7 miRNA. Moreover, molecular and genetic analyses demonstrate that the levels of
lsy-6 expression and mature
let-7, miR-58, and miR-62 are significantly reduced in
teg-1 mutants, suggesting mutations in
teg-1 affect the levels of a broad range of miRNA members. We also found that both VIG-1 and ALG-1 protein levels are reduced in
teg-1 mutants, although their mRNA levels remain unchanged. Together, these findings suggest that the association of TEG-1 with miRISC is necessary for miRNAs to function properly during development. We further demonstrate that the human orthologs of TEG-1, VIG-1 and ALG-1 (CD2BP2, SERBP1/PAI-RBP1, and AGO2) complex in HeLa cells, and knockdown of CD2BP2 results in reduced
let-7a miRNA levels. Therefore, TEG-1's role in affecting miRNA levels and function is likely conserved from nematodes to humans. We propose that TEG-1 CD2BP2 stabilizes miRISC and mature miRNAs, maintaining them at levels necessary to properly regulate target gene expression.