Identifying mRNA sequence elements for target recognition by human Argonaute proteins

Li, Jingjing; Kim, TaeHyung; Nutiu, Razvan; Ray, Debashish; Hughes, Timothy R.; Zhang, Zhaolei

doi:10.1101/gr.162230.113

Cited by 34 publications

(31 citation statements)

References 31 publications

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“…Our results indicated that the sequence motifs resulting from DeBooster agreed well with those reported in the literature (Fig 2d). For example, the binding sequence motif of AGO2 computed by DeBooster was enriched with A, U and C but depleted of G, which was consistent with the previous study [28]. PTB, as indicated by its name (polypyrimidine tract-binding protein), mainly binds to the U/C-rich regions [29], which was also reflected in the sequence motif derived from DeBooster.…”

Section: Debooster Captures the Sequence Preferences Of Rbp Bindingsupporting

confidence: 89%

A Deep Boosting Based Approach for Capturing the Sequence Binding Preferences of RNA-Binding Proteins from High-Throughput CLIP-Seq Data

Dong

et al. 2016

Preprint

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(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/086421 doi: bioRxiv preprint first posted online Nov. 8, 2016; tions of RBPs, including the binding effects of the RNA helicase MOV10 on mRNA degradation, the influence of different binding behaviors of the ADAR proteins on RNA editing, as well as the antagonizing effect of RBP binding on miRNA repression. Moreover, DeBooster may provide an effective index to investigate the effect of pathogenic mutations in RBP binding sites, especially those related to splicing events. We expect that DeBooster will be widely applied to analyze large-scale CLIP-seq experimental data and can provide a practically useful tool for novel biological discoveries in understanding the regulatory mechanisms of RBPs.

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Section: Debooster Captures the Sequence Preferences Of Rbp Bindingsupporting

confidence: 89%

A Deep Boosting Based Approach for Capturing the Sequence Binding Preferences of RNA-Binding Proteins from High-Throughput CLIP-Seq Data

Dong

et al. 2016

Preprint

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“…Similar results have also been shown by the RNA immunoprecipitation experiments in Zhao et al (14). Similarly, a recent study reports that Argonaute proteins have sequence specificity in the absence of microRNAs (39). In addition, Piwil1 regulates mRNA translation (40), one of key regulatory mechanisms in neocortical development (5,12).…”

Section: Discussionsupporting

confidence: 79%

Multiple roles of PIWIL1 in mouse neocorticogenesis

Viljetić

Diao

Liu

et al. 2017

Preprint

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PIWI-interacting RNAs (piRNAs) and their associated PIWI proteins play an important role in repressing transposable elements in animal germlines. However, little is known about the function of PIWI proteins and piRNAs in the developing brain. Here, we investigated the role of an important PIWI family member, Piwi-like protein 1 (Piwil1; also known as Miwi in mouse) in the developing mouse neocortex. Using a Piwil1 knock-out (Piwil1 KO) mouse strain, we found that Piwil1 is essential for several steps of neocorticogenesis, including neocortical cell cycle, neuron migration and dendritogenesis. Piwil1 deletion resulted in increased cell cycle re-entry at embryonic day 17 (E17) when predominantly intracortically projecting neurons are being produced. Prenatal Piwil1 deletion increased the number of Pax6+ radial glia at postnatal day 0 (P0). Furthermore, Piwil1 deletion disrupted migration of Satb2+ neurons within deep layers at E17, P0 and P7. Satb2+ neurons showed increased co-localization with Bcl11b (also known as Ctip2), marker of subcortically projecting neurons. Piwil1 knockouts had disrupted neocortical circuitry represented by thinning of the corpus callosum and altered dendritogenesis. We further investigated if Piwil1 deletion disrupted expression levels of neocortical piRNAs by small RNA-sequencing in neocortex. We did not find differential expression of piRNAs in the neocortices of Piwil1 KO, while differences were observed in other Piwil1 KO tissues. This result suggests that Piwil1 may act independently of piRNAs and have novel roles in higher cognitive centers, such as neocortex. In addition, we report a screen of piRNAs derived from tRNA fragments in developing neocortices. Our result is the first report of selective subsets of piRNAs and tRNA fragments in developing prenatal neocortices and helps clarify some outstanding questions about the role of the piRNA pathway in the brain.peer-reviewed)

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“…AGO2, a second subunit of RISC, was also among the proteins most significantly bound to HPAT5. This result was surprising, as it is commonly known that miRNAs are required to guide RISC to target RNAs, despite recent reports that have consistently observed AGO2-RNA associations independent of miRNAs 37 .…”

Section: Resultsmentioning

confidence: 84%

The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear reprogramming

et al. 2015

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Long intergenic noncoding RNAs (lincRNAs) are derived from thousands of loci in mammalian genomes and are frequently enriched in transposable elements (TEs). Although families of TE-derived lincRNAs have recently been implicated in the regulation of pluripotency, little is known of the specific functions of individual family members. Here we characterize three new individual TE-derived human lincRNAs, human pluripotency-associated transcripts 2, 3 and 5 (HPAT2, HPAT3 and HPAT5). Loss-of-function experiments indicate that HPAT2, HPAT3 and HPAT5 function in preimplantation embryo development to modulate the acquisition of pluripotency and the formation of the inner cell mass. CRISPR-mediated disruption of the genes for these lincRNAs in pluripotent stem cells, followed by whole-transcriptome analysis, identifies HPAT5 as a key component of the pluripotency network. Protein binding and reporter-based assays further demonstrate that HPAT5 interacts with the let-7 microRNA family. Our results indicate that unique individual members of large primate-specific lincRNA families modulate gene expression during development and differentiation to reinforce cell fate.

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Identifying mRNA sequence elements for target recognition by human Argonaute proteins

Cited by 34 publications

References 31 publications

A Deep Boosting Based Approach for Capturing the Sequence Binding Preferences of RNA-Binding Proteins from High-Throughput CLIP-Seq Data

A Deep Boosting Based Approach for Capturing the Sequence Binding Preferences of RNA-Binding Proteins from High-Throughput CLIP-Seq Data

Multiple roles of PIWIL1 in mouse neocorticogenesis

The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear reprogramming

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