MicroRNAs: regulators of neuronal fate

Sun, Alfred Xuyang; Crabtree, Robert H.; Yoo, Andrew S.

doi:10.1016/j.ceb.2012.12.007

Cited by 153 publications

(119 citation statements)

References 58 publications

(45 reference statements)

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“…We assessed all 7-mers for evidence of conservation above background among our 2035 mouse 39 UTR extensions. Notably, the motifs with highest signals and highest numbers of conserved instances corresponded to seeds for miRNAs with welldescribed neural functions (Sun et al 2013), including let-7, miR-124, miR-9, miR-96, miR-125, and miR-137 (Fig. 7A).…”

Section: Novel 39 Utr Extensions Harbor Thousands Of Conserved Mirna mentioning

confidence: 99%

Widespread and extensive lengthening of 3′ UTRs in the mammalian brain

et al. 2013

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Remarkable advances in techniques for gene expression profiling have radically changed our knowledge of the transcriptome. Recently, the mammalian brain was reported to express many long intergenic noncoding (lincRNAs) from loci downstream from protein-coding genes. Our experimental tests failed to validate specific accumulation of lincRNA transcripts, and instead revealed strongly distal 3′ UTRs generated by alternative cleavage and polyadenylation (APA). With this perspective in mind, we analyzed deep mammalian RNA-seq data using conservative criteria, and identified 2035 mouse and 1847 human genes that utilize substantially distal novel 3′ UTRs. Each of these extends at least 500 bases past the most distal 3′ termini available in Ensembl v65, and collectively they add 6.6 Mb and 5.1 Mb to the mRNA space of mouse and human, respectively. Extensive Northern analyses validated stable accumulation of distal APA isoforms, including transcripts bearing exceptionally long 3′ UTRs (many >10 kb and some >18 kb in length). The Northern data further illustrate that the extensions we annotated were not due to unprocessed transcriptional run-off events. Global tissue comparisons revealed that APA events yielding these extensions were most prevalent in the mouse and human brain. Finally, these extensions collectively contain thousands of conserved miRNA binding sites, and these are strongly enriched for many well-studied neural miRNAs. Altogether, these new 3′ UTR annotations greatly expand the scope of post-transcriptional regulatory networks in mammals, and have particular impact on the central nervous system.

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Section: Novel 39 Utr Extensions Harbor Thousands Of Conserved Mirna mentioning

confidence: 99%

Widespread and extensive lengthening of 3′ UTRs in the mammalian brain

et al. 2013

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“…It is expressed in postmitotic neurons in all CNS regions, except the pituitary gland, and is developmentally regulated; its expression is very low in progenitor cells, but it progressively increases during prenatal period reaching at the highest level in postnatal brain. Several studies have shown that [12,13]]. …”

Section: Potential Role Of Mir-124 In Neuronal Differentiation Stresmentioning

confidence: 99%

microRNA-124: a putative therapeutic target and biomarker for major depression

Dwivedi

2017

Expert Opinion on Therapeutic Targets

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“…Small RNAs such as microRNAs (miRNAs) have been shown to affect neural differentiation (1,2) but their roles in the control of behaviour are only beginning to be explored.…”

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confidence: 99%

MicroRNA-encoded behavior in Drosophila

Picao-Osorio

Johnston

Landgraf

et al. 2015

Science

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The relationship between microRNA regulation and the specification of behaviour is only beginning to be explored. Here we find that mutation of a single microRNA locus (miR-iab4/8) in Drosophila larvae affects the animal' s capacity to correct its orientation if turned upside-down (self-righting). One of the microRNA targets involved in this behaviour is the Hox gene Ultrabithorax whose derepression in two metameric neurons leads to self-righting defects. In vivo neural activity analysis reveals that these neurons, the self-righting node (SRN), have different activity patterns in wild type and miRNA mutants whilst thermogenetic manipulation of SRN activity results in changes in self-righting behaviour. Our work thus reveals a microRNA-encoded behaviour and suggests that other microRNAs might also be involved in behavioural control in Drosophila and other species.The regulation of RNA expression and function is emerging as a hub for gene expression control across a variety of cellular and physiological contexts including neural development and specification. Small RNAs such as microRNAs (miRNAs) have been shown to affect neural differentiation (1, 2) but their roles in the control of behaviour are only beginning to be explored.Previous work in our laboratory focused on the mechanisms and impact of RNA regulation on the expression and neural function of the Drosophila Hox genes (3-6). These genes encode a family of evolutionarily conserved transcription factors that control specific programs of neural differentiation along the body axis (7-9) offering an opportunity to investigate how RNA regulation relates to the formation of complex tissues such as the nervous system.Here we use the Hox gene system to investigate the roles played by a single miRNA locus (miR-iab4/8) (3,(10)(11)(12)(13)(14)30) on the specification of the nervous system during early Drosophila development. This miRNA locus controls the embryonic expression of posterior Hox genes (3,(10)(11)(12)(13)(14). Given that we found no detectable differences in the morphological layout of the main components of the nervous system in late Drosophila embryos of wild + This manuscript has been accepted for publication in Science. This version has not undergone final editing. Please refer to the complete version of record at http://www.sciencemag.org/. The manuscript may not be reproduced or used in any manner that does not fall within the fair use provisions of the Copyright Act without the prior, written permission of AAAS. * Correspondence to: Claudio R. Alonso c.alonso@sussex.ac.uk. (13)) (Fig S3B-F) we analysed early larval behaviour as a stratagem to probe the functional integrity of the late embryonic nervous system. Europe PMC Funders GroupMost behaviours in early larva were unaffected by the miRNA mutation ( Fig. S1, movie S1 and S2) except self-righting (SR) behaviour ( Fig. 1A-C, movies S3-S4): miRNA mutant larvae were unable to return to their normal orientation at the same speed as their wild type counterparts.By means of selective target ...

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MicroRNAs: regulators of neuronal fate

Cited by 153 publications

References 58 publications

Widespread and extensive lengthening of 3′ UTRs in the mammalian brain

Widespread and extensive lengthening of 3′ UTRs in the mammalian brain

microRNA-124: a putative therapeutic target and biomarker for major depression

MicroRNA-encoded behavior in Drosophila

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