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Recently Evolved Tumor Suppressor Transcript TP73-AS1 Functions as Sponge of
Human-Specific miR-941
#MMPMID29474580
Hu H
; Liu JM
; Hu Z
; Jiang X
; Yang X
; Li J
; Zhang Y
; Yu H
; Khaitovich P
Mol Biol Evol
2018[May]; 35
(5
): 1063-1077
PMID29474580
show ga
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.
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