The code within the code: microRNAs target coding regions

Forman, Joshua J.; Coller, Hilary A.

doi:10.4161/cc.9.8.11202

Cited by 142 publications

(103 citation statements)

References 80 publications

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“…We therefore developed an algorithm, MinoTar (www.minotar.csail.mit.edu), to identify conserved regulatory motifs specifically within proteincoding regions. Our approach shares some similarity with that taken recently in vertebrates by Forman et al (18,24), but additionally allows for the scoring of sites not perfectly conserved across all species in the alignment. Because a significant majority (70% or more) of highly preferentially conserved sites are not perfectly conserved, this allows for the confident prediction of a substantially increased set of targets and a more comprehensive comparison to the extent of targeting in 3′UTRs.…”

mentioning

confidence: 78%

Conserved microRNA targeting in Drosophila is as widespread in coding regions as in 3′UTRs

Schnall-Levin

Zhao

Perrimon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

148

131

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MicroRNAs (miRNAs) are a class of short noncoding RNAs that regulate protein-coding genes posttranscriptionally. In animals, most known miRNA targeting occurs within the 3′UTR of mRNAs, but the extent of biologically relevant targeting in the ORF or 5′ UTR of mRNAs remains unknown. Here, we develop an algorithm (MinoTar-miRNA ORF Targets) to identify conserved regulatory motifs within protein-coding regions and use it to estimate the number of preferentially conserved miRNA-target sites in ORFs. We show that, in Drosophila, preferentially conserved miRNA targeting in ORFs is as widespread as it is in 3′UTRs and that, while far less abundant, conserved targets in Drosophila 5′UTRs number in the hundreds. Using our algorithm, we predicted a set of high-confidence ORF targets and selected seven miRNA-target pairs from among these for experimental validation. We observed downregulation by the miRNA in five out of seven cases, indicating our approach can recover functional sites with high confidence. Additionally, we observed additive targeting by multiple sites within a single ORF. Altogether, our results demonstrate that the scale of biologically important miRNA targeting in ORFs is extensive and that computational tools such as ours can aid in the identification of such targets. Further evidence suggests that our results extend to mammals, but that the extent of ORF and 5′UTR targeting relative to 3′UTR targeting may be greater in Drosophila.comparative genomics | target prediction

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mentioning

confidence: 78%

Conserved microRNA targeting in Drosophila is as widespread in coding regions as in 3′UTRs

Schnall-Levin

Zhao

Perrimon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

148

131

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show abstract

“…microRNAs (miRNAs) are a group of non-coding RNAs (~22 nt) that can silence gene expression by binding to the 3′ untranslated region (UTR) or to the coding region of target mRNAs to promote mRNA destabilization or inhibit protein translation [5,6]. Importantly, many miRNAs have been shown to be expressed in hematopoietic lineages and to act as pivotal regulators of transcriptional programs for normal hematopoiesis, including HSC self-renewal, differentiation and functioning [7,8].…”

Section: Introductionmentioning

confidence: 99%

miR-142-3p regulates the formation and differentiation of hematopoietic stem cells in vertebrates

et al. 2013

Cell Res

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Previous studies on developmental hematopoiesis have mainly focused on signaling and transcription factors, while the appreciation of epigenetic regulation including that of microRNAs is recent. Here, we show that in zebrafish and mouse, miR-142-3p is specifically expressed in hematopoietic stem cells (HSCs). Knockdown of miR-142a-3p in zebrafish led to a reduced population of HSCs in the aorta-gonad-mesonephros (AGM) region as well as T-cell defects in the thymus. Mechanistically, miR-142a-3p regulates HSC formation and differentiation through the repression of interferon regulatory factor 7 (irf7)-mediated inflammation signaling. Finally, we show that miR-142-3p is also involved in the development of HSCs in mouse AGM, suggesting that it has a highly conserved role in vertebrates. Together, these findings unveil the pivotal roles that miR-142a-3p plays in the formation and differentiation of HSCs by repressing irf7 signaling.

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“…miRNAs interact primarily with the 3'-untranslated (3'UTR) region of their target mRNAs, although recent evidences show that miRNAs can also associate with sites located within the coding region of target genes [22]. In fact, complex arrays of multiple binding sites for either the same or different miRNAs located both in the 3'UTR as well as in the coding region of the target genes have been reported [23].…”

Section: Mirna Target Bindingmentioning

confidence: 99%

miRNAs as Essential Mediators of the Actions of Retinoic Acid in Neuroblastoma Cells

Meseguer¹,

Escamilla²,

Barettino³

2013

Neuroblastoma

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The code within the code: microRNAs target coding regions

Cited by 142 publications

References 80 publications

Conserved microRNA targeting in Drosophila is as widespread in coding regions as in 3′UTRs

Conserved microRNA targeting in Drosophila is as widespread in coding regions as in 3′UTRs

miR-142-3p regulates the formation and differentiation of hematopoietic stem cells in vertebrates

miRNAs as Essential Mediators of the Actions of Retinoic Acid in Neuroblastoma Cells

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