Recently evolved tumor suppressor transcript TP73-AS1 functions as sponge of 
human-specific miR-941

Hu, Haiyang; Liu, Jian-Mei; Hu, Zhenyu; Jiang, Xi; Yang, Xiaode; Li, Jiangxia; Zhang, Yao; Yu, Haijing; Khaitovich, Philipp

doi:10.1093/molbev/msy022

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Recently evolved tumor suppressor transcript TP73-AS1 functions as sponge of human-specific miR-941

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Khaitovich, Philipp
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Citation

Hu, H., Liu, J.-M., Hu, Z., Jiang, X., Yang, X., Li, J., et al. (2018). Recently evolved tumor suppressor transcript TP73-AS1 functions as sponge of human-specific miR-941. Molecular Biology and Evolution, 35(5), 1063-1077. doi:10.1093/molbev/msy022.

Cite as: https://hdl.handle.net/21.11116/0000-0001-66AA-D

Abstract

MicroRNA (miRNA) sponges are vital components of posttranscriptional gene regulation. Yet, only a limited number of miRNA sponges have been identified. Here, we show that the recently evolved noncoding tumor suppressor transcript, antisense RNA to TP73 gene (TP73-AS1), functions as a natural sponge of human-specific miRNA miR-941. We find unusually nine high-affinity miR-941 binding sites clustering within 1 kb region on TP73-AS1, which forms miR-941 sponge region. This sponge region displays increased sequence constraint only in humans, and its formation can be traced to the tandem expansion of a 71-nt-long sequence containing a single miR-941 binding site in old world monkeys. We further confirm TP73-AS1 functions as an efficient miR-941 sponge based on massive transcriptome data analyses, wound-healing assay, and Argonaute protein immunoprecipitation experiments conducted in cell lines. The expression of miR-941 and its sponge correlate inversely across multiple healthy and cancerous tissues, with miR-941 being highly expressed in tumors and preferentially repressing tumor suppressors. Thus, the TP73-AS1 and miR-941 duo represents an unusual case of the extremely rapid evolution of noncoding regulators controlling cell migration, proliferation, and tumorigenesis.