%0 Journal Article
%A Hu, Haiyang
%A Liu, Jian-Mei
%A Hu, Zhenyu
%A Jiang, Xi
%A Yang, Xiaode
%A Li, Jiangxia
%A Zhang, Yao
%A Yu, Haijing
%A Khaitovich, Philipp
%+ Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T Recently evolved tumor suppressor transcript TP73-AS1 functions as sponge of human-specific miR-941 : 
%G eng
%U https://hdl.handle.net/21.11116/0000-0001-66AA-D
%R 10.1093/molbev/msy022
%7 2018-02-20
%D 2018
%8 01.05.2018
%* Review method: peer-reviewed
%X 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.
%K microRNA sponge, young noncoding RNA, co-evolution, tumorigenesis
%J Molecular Biology and Evolution
%O Mol. Biol. Evol.
%V 35
%N 5
%& 1063
%P 1063 - 1077
%I Oxford University Press
%C Oxford
%@ 0737-4038