% pubman genre = article @article{item_2596433, title = {{Recently evolved tumor suppressor transcript TP73-AS1 functions as sponge of human-specific miR-941}}, author = {Hu, Haiyang and Liu, Jian-Mei and Hu, Zhenyu and Jiang, Xi and Yang, Xiaode and Li, Jiangxia and Zhang, Yao and Yu, Haijing and Khaitovich, Philipp}, language = {eng}, issn = {0737-4038}, doi = {10.1093/molbev/msy022}, publisher = {Oxford University Press}, address = {Oxford}, year = {2018}, date = {2018-05-01}, 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.}}, journal = {{Molecular Biology and Evolution}}, volume = {35}, number = {5}, pages = {1063--1077}, }