A sliding-bulge structure at the Dicer processing site of pre-miRNAs regulates alternative Dicer processing to generate 5'-isomiRs

Hongming Ma; Yonggan Wu; Qi Niu; Junli Zhang; Gengxiang Jia; N Manjunath; Haoquan Wu

doi:10.1016/j.heliyon.2016.e00148

A sliding-bulge structure at the Dicer processing site of pre-miRNAs regulates alternative Dicer processing to generate 5'-isomiRs

Heliyon. 2016 Sep 1;2(9):e00148. doi: 10.1016/j.heliyon.2016.e00148. eCollection 2016 Sep.

Authors

Hongming Ma¹, Yonggan Wu², Qi Niu³, Junli Zhang¹, Gengxiang Jia¹, N Manjunath¹, Haoquan Wu¹

Affiliations

¹ Center of Emphasis in Infectious Disease, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA.
² Labii Inc., Mountain View, CA 94043, USA.
³ Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.

Abstract

5'-isomiRs expand the repertoire of miRNA targets. However, how they are generated is not well understood. Previously, we showed that for some miRNAs in mammalian cells, Drosha cleaves at multiple sites to generate multiple pre-miRNAs that give rise to multiple 5'-isomiRs. Here, we showed that for some other miRNAs, 5'-isomiRs are generated by alternative Dicer processing. In addition, we showed that in miR-203, alternative Dicer processing is regulated by a conserved sliding-bulge structure at the Dicer processing site, which allows the pre-miRNA molecule to fold into two different structures that are processed differently by Dicer. So far no RNA motif that slides to change conformation and alter a protein-RNA interaction has been reported. Thus, our study revealed a novel RNA motif that regulates 5'-isomiR generation in some miRNAs. It might also contribute to regulating protein-RNA interactions in other biological processes, since it takes only one point mutation to generate the sliding bulge, and there are a large number of different RNAs in the cell.

Keywords: Biological sciences; Cell biology; Genetics.