MicroRNA Target Recognition: Insights from Transcriptome-Wide Non-Canonical Interactions.
MicroRNAs (miRNAs) are small non-coding RNAs (∼22 nucleotides) regulating gene expression at the post-transcriptional level. By directing the RNA-induced silencing complex (RISC) to bind specific target mRNAs, miRNA can repress target genes and affect various biological phenotypes. Functional miRNA target recognition is known to majorly attribute specificity to consecutive pairing with seed region (position 2-8) of miRNA. Recent advances in a transcriptome-wide method of mapping miRNA binding sites (Ago HITS-CLIP) elucidated that a large portion of miRNA-target interactions in vivo are mediated not only through the canonical "seed sites" but also via non-canonical sites (∼15-80%), setting the stage to expand and determine their properties. Here we focus on recent findings from transcriptome-wide non-canonical miRNA-target interactions, specifically regarding "nucleation bulges" and "seed-like motifs". We also discuss insights from Ago HITS-CLIP data alongside structural and biochemical studies, which highlight putative mechanisms of miRNA target recognition, and the biological significance of these non-canonical sites mediating marginal repression.
Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
Heeyoung
H
Seok
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, Korea.
Juyoung
J
Ham
EncodeGEN Co. Ltd., Seoul 06329, Korea.
Eun-Sook
ES
Jang
Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
Sung Wook
SW
Chi
D020413:3' Untranslated Regions; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D059467:Transcriptome
D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger
CLIP; argonaute; microRNA; non-canonical targets