RT Journal
A1 Wolter, Justin M.
A1 Le, Hoai Huang Thi
A1 Linse, Alexander
A1 Godlove, Victoria A.
A1 Nguyen, Thuy-Duyen
A1 Kotagama, Kasuen
A1 Lynch, Alissa
A1 Rawls, Alan
A1 Mangone, Marco
T1 Evolutionary patterns of metazoan microRNAs reveal targeting principles in the let-7 and miR-10 families
JF Genome Research 
JO Genome Research 
YR 2017 
FD January 01 
VO 27 
IS 1 
SP 53 
OP 63 
DO 10.1101/gr.209361.116 
UL http://genome.cshlp.org/content/27/1/53.abstract 
AB MicroRNAs (miRNAs) regulate gene output by targeting degenerate elements in mRNAs and have undergone drastic expansions in higher metazoan genomes. The evolutionary advantage of maintaining copies of highly similar miRNAs is not well understood, nor is it clear what unique functions, if any, miRNA family members possess. Here, we study evolutionary patterns of metazoan miRNAs, focusing on the targeting preferences of the let-7 and miR-10 families. These studies reveal hotspots for sequence evolution with implications for targeting and secondary structure. High-throughput screening for functional targets reveals that each miRNA represses sites with distinct features and regulates a large number of genes with cooperative function in regulatory networks. Unexpectedly, given the high degree of similarity, single-nucleotide changes grant miRNA family members with distinct targeting preferences. Together, our data suggest complex functional relationships among miRNA duplications, novel expression patterns, sequence change, and the acquisition of new targets.