MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35191832.
- Also identified by DOI 10.7554/eLife.69803 and PMC identifier 8940178.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
MicroRNAs (miRNAs), in association with Argonaute (AGO) proteins, direct repression by pairing to sites within mRNAs. Compared to pairing preferences of the miRNA seed region (nucleotides 2-8), preferences of the miRNA 3' region are poorly understood, due to the sparsity of measured affinities for the many pairing possibilities. We used RNA bind-n-seq with purified AGO2-miRNA complexes to measure relative affinities of >1000 3'-pairing architectures for each miRNA. In some cases, optimal 3' pairing increased affinity by >500 fold. Some miRNAs had two high-affinity 3'-pairing modes-one of which included additional nucleotides bridging seed and 3' pairing to enable high-affinity pairing to miRNA nucleotide 11. The affinity of binding and the position of optimal pairing both tracked with the occurrence of G or oligo(G/C) nucleotides within the miRNA. These and other results advance understanding of miRNA targeting, providing insight into how optimal 3' pairing is determined for each miRNA.
Medical subject headings
- MicroRNAs