研究異質性核糖核酸蛋白Q 在let-7/TRIM71路徑中所扮演的角色

Abstract

The let-7 microRNA is an evolutionarily conserved microRNA that down regulates gene expression by co-operating with RNA induced silencing complex (RISC). In C. elegans, the let-7 miRNA starts to express at the larva 3 (L3) stage of and continuously accumulates through the L4 stage, leading to cell differentiation that is crucial to the L4-to-adult transition. Mutations in let-7 results in developmental phenotypes, such as vulva bursting and the abnormality of seam cell proliferation and differentiation. Previously, by RNAi screening, we found that depleting an RNA binding protein, hrp-2, suppressed phenotypes of hypomorphic and temperature-sensitive let-7(n2853) mutant allele, which contains a G-to-A point mutation at the let-7 seed region sequence. let-7 miRNA regulates C. elegans L4/adult transition by targeting lin-41 3' UTR. Down regulation of lin-41 allows expression of genes for C. elegans maturation. This regulation has been demonstrated to be an evolutionarily conserved pathway from the nematode to human, in which TRIM71, the lin-41 homolog, is regulated by human let-7 miRNA. Here, we knocked down hnRNP Q, the hrp-2 homolog, expression in human hepatocellular carcinoma cells and, interestingly detected decreased expression of TRIM7, the human homolog of lin-41, and Lin28B, the negative regulator of let-7 biogenesis. We found that the let-7 miRNA levels increased in hnRNP Q depleted HuH7 cells, as well as HEK293T cells, which may link to reduced activity of lin41 3' UTR luciferase reporter. Expressing RNAi-resistant hnRNP Q vectors in those cells partially restores effects of hnRNP Q depletion. Although the mechanism underlying for hnRNP Q modulating the let-7/TRIM71 regulation and LIN28B expression remains unclear, our findings indicate that hnRNP Q may regulate the let-7/TRIM71 pathway by affecting let-7 miRNA biogenesis.