High-resolution <i>in vivo</i> identification of miRNA targets by Halo-Enhanced Ago2 Pulldown

Li, Xiaohua; Pritykin, Yuri; Concepcion, Carla P.; Lu, Yuheng; Rocca, Gaspare La; Zhang, Minsi; Cook, Peter J.; Au, Yu Wah; Popow, Olesja; Paulo, João A.; Otis, Hannah G.; Mastroleo, Chiara; Ogrodowski, Paul; Schreiner, Ryan; Haigis, Kevin M.; Betel, Doron; Leslie, Christina; Ventura, Andrea

doi:10.1101/820548

Cited by 2 publications

(2 citation statements)

References 74 publications

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“…This element corresponds to a miR-25/92 family seed match ( Fig. 2c) and was recently shown to be bound and regulated by members of the miR-25/92 family in mouse embryonic heart [22]. At the 3′ end of Cyrano, one conserved element (GCAAUAAA) corresponds to the Cyrano polyadenylation signal (PAS) as well as a miR-137 site.…”

Section: Lncloom Identifies Deeply Conserved Elements In the Cyrano Lmentioning

confidence: 95%

Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences

et al. 2021

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Background Animal genomes contain thousands of long noncoding RNA (lncRNA) genes, a growing subset of which are thought to be functionally important. This functionality is often mediated by short sequence elements scattered throughout the RNA sequence that correspond to binding sites for small RNAs and RNA binding proteins. Throughout vertebrate evolution, the sequences of lncRNA genes changed extensively, so that it is often impossible to obtain significant alignments between sequences of lncRNAs from evolutionary distant species, even when synteny is evident. This often prohibits identifying conserved lncRNAs that are likely to be functional or prioritizing constrained regions for experimental interrogation. Results We introduce here LncLOOM, a novel algorithmic framework for the discovery and evaluation of syntenic combinations of short motifs. LncLOOM is based on a graph representation of the input sequences and uses integer linear programming to efficiently compare dozens of sequences that have thousands of bases each and to evaluate the significance of the recovered motifs. We show that LncLOOM is capable of identifying specific, biologically relevant motifs which are conserved throughout vertebrates and beyond in lncRNAs and 3′UTRs, including novel functional RNA elements in the CHASERR lncRNA that are required for regulation of CHD2 expression. Conclusions We expect that LncLOOM will become a broadly used approach for the discovery of functionally relevant elements in the noncoding genome.

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Section: Lncloom Identifies Deeply Conserved Elements In the Cyrano Lmentioning

confidence: 95%

Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences

et al. 2021

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“…(Hafner et al 2010)) and in vivo (i.e. (Li et al 2019)). Experimental evidence for AGO-binding greatly increases the accuracy of miRNA target predictions.…”

Section: Introductionmentioning

confidence: 99%

Noncanonical targeting contributes significantly to miRNA-mediated regulation

Tan

Abdulkarim

Marques

2020

Preprint

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ABSTRACTDetermining which genes are targeted by miRNAs is crucial to elucidate their contributions to diverse biological processes in health and disease. Most miRNA target prediction tools rely on the identification of complementary regions between transcripts and miRNAs. Whereas important for target recognition, the presence of complementary sites is not sufficient to identify transcripts targeted by miRNAs.Here, we describe an unbiased statistical genomics approach that explores genetically driven changes in gene expression between human individuals. Using this approach, we identified transcripts that respond to physiological changes in miRNA levels. We found that a much smaller fraction of mRNAs expressed in lymphoblastoid cell lines (LCLs) than what is predicted by other tools is targeted by miRNAs. We estimate that each miRNA has a relatively small number of targets. The transcripts we predict to be miRNA targets are enriched in AGO-binding and previously validated miRNAs target interactions, supporting the reliability of our predictions. Consistent with previous analysis, these targets are also enriched among dosage sensitive and highly controlled genes.Almost a third of genes we predict to be miRNA targets lack sequence complementarity to the miRNA seed region (noncanonical targets). These noncanonical targets have higher complementary with the miRNA 3’ end. The impact of miRNAs on the levels of their canonical or noncanonical targets is identical supporting the relevance of this poorly explored mechanism of targeting.

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High-resolution in vivo identification of miRNA targets by Halo-Enhanced Ago2 Pulldown

Cited by 2 publications

References 74 publications

Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences

Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences

Noncanonical targeting contributes significantly to miRNA-mediated regulation

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