Ligation of 2 ', 3 '-cyclic phosphate RNAs for the identification of microRNA binding sites


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Date

2021-01

Publication Type

Journal Article

ETH Bibliography

yes

Citations

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Data

Abstract

Identifying the targetome of a microRNA is key for understanding its functions. Cross‐linking and immunoprecipitation (CLIP) methods capture native miRNA‐mRNA interactions in cells. Some of these methods yield small amounts of chimeric miRNA‐mRNA sequences via ligation of 5′‐phosphorylated RNAs produced during the protocol. Here, we introduce chemically synthesized microRNAs (miRNAs) bearing 2′‐, 3′‐cyclic phosphate groups, as part of a new CLIP method that does not require 5′‐phosphorylation for ligation. We show in a system that models miRNAs bound to their targets, that addition of recombinant bacterial ligase RtcB increases ligation efficiency, and that the transformation proceeds via a 3′‐phosphate intermediate. By optimizing the chemistry underlying ligation, we provide the basis for an improved method to identify miRNA targetomes.

Publication status

published

Editor

Book title

Journal / series

Volume

595 (2)

Pages / Article No.

230 - 240

Publisher

Wiley

Event

Edition / version

Methods

Software

Geographic location

Date collected

Date created

Subject

2 ',3 '-cyclic phosphate; CLIP; ligation; microRNA; RtcB

Organisational unit

03760 - Hall, Jonathan / Hall, Jonathan check_circle

Notes

Funding

169612 - Chemical Approaches to Functionalize Human microRNAs (SNF)

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