MicroRNA Clustering Assists Processing of Suboptimal MicroRNA Hairpins Through the Action of the ERH Protein. Fang and Bartel

Published: 4 April 2020| Version 2 | DOI: 10.17632/fghs5z4yp4.2
David Bartel, Wenwen Fang


Microprocessor initiates processing of microRNAs (miRNAs) from hairpin regions of primary transcripts (pri-miRNAs). Pri-miRNAs often contain multiple miRNA hairpins, and this clustered arrangement can assist processing of otherwise defective hairpins. We find that miR-451, which derives from a hairpin with a suboptimal terminal loop and a suboptimal stem length, accumulates to 40-fold higher levels when clustered with a helper hairpin. This phenomenon tolerates changes in hairpin order, linker lengths, and the identities of the helper hairpin, the recipient hairpin, the linker-sequence, and the RNA polymerase that transcribes the hairpins. It can act reciprocally and need not occur co-transcriptionally. It requires Microprocessor recognition of the helper hairpin and linkage of the two hairpins, yet predominantly manifests after helper-hairpin processing. It also requires enhancer of rudimentary homolog (ERH), which copurifies with Microprocessor and can dimerize and interact with other proteins that can dimerize, suggesting a model in which one Microprocessor recruits another Microprocessor.



Whitehead Institute for Biomedical Research


Molecular Biology