miRNA-independent function of long noncoding pri-miRNA loci
Daniel He, David Wu, Sören Müller, Lin Wang, Parna Saha, Sajad Hamid Ahanger, Siyuan Liu, Miao Cui, Sung Jun Hong, Miten Jain, Hugh E. Olson, Mark Akeson, J Costello, Aarón Díaz, Daniel A. Lim
Abstract
Significance The human genome contains many thousands of genes that produce a large diversity of long noncoding RNAs (lncRNAs). Some lncRNA genes produce microRNAs (miRNAs), which are regulators of protein expression. It has been unclear whether lncRNA genes that produce miRNAs, termed lnc-pri-miRNAs, have important function independent of their miRNAs. We find multiple lnc-pri-miRNA genes that regulate cell proliferation even when miRNA production machinery is knocked down. lnc-pri-miRNA LOC646329 produces miR-29a/b1, and the function of LOC646329 in cell proliferation can be genetically and phenotypically separated from its cognate miRNAs. The miRNA-independent function of LOC646329 and other lnc-pri-miRNAs relates to their activation of genes in physical proximity. These results shed light on the function and intermingled complexity of the noncoding genome.