A Resource for the Conditional Ablation of microRNAs in the Mouse

Park, Chong Yon; Jeker, Lukas T.; Carver-Moore, Karen; Oh, Alyssia; Liu, Huey Jiin; Cameron, Rachel; Richards, Hunter W.; Li, Zhongmei; Adler, David A.; Yoshinaga, Yuko; Martínez, María Rodríguez; Nefadov, Michael; Abbas, Abul K.; Weiss, Art; Lanier, Lewis L.; Jong, Pieter J. de; Bluestone, Jeffrey A.; Srivastava, Deepak; McManus, Michael T.

doi:10.1016/j.celrep.2012.02.008

Cited by 165 publications

(169 citation statements)

References 33 publications

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“…The diverse networks through which miRNAs exert their biological functions in development, differentiation and disease are only beginning to be elucidated. The effect of miRNA gene knockout is often not obvious in the phenotype under normal conditions, [151][152][153][154][155] only to become apparent in certain cellular contexts or under stress conditions, highlighting the importance of miRNA in the 'micromanagement' of gene expression. More questions remain about the specific protein interactions that are involved in the inhibition of translational initiation by miRNAs.…”

Section: Resultsmentioning

confidence: 99%

The complexity of miRNA-mediated repression

2014

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Since their discovery 20 years ago, miRNAs have attracted much attention from all areas of biology. These short (B22 nt) non-coding RNA molecules are highly conserved in evolution and are present in nearly all eukaryotes. They have critical roles in virtually every cellular process, particularly determination of cell fate in development and regulation of the cell cycle. Although it has long been known that miRNAs bind to mRNAs to trigger translational repression and degradation, there had been much debate regarding their precise mode of action. It is now believed that translational control is the primary event, only later followed by mRNA destabilisation. This review will discuss the most recent advances in our understanding of the molecular underpinnings of miRNA-mediated repression. Moreover, we highlight the multitude of regulatory mechanisms that modulate miRNA function.

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Section: Resultsmentioning

confidence: 99%

The complexity of miRNA-mediated repression

2014

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“…Given that p19 Arf regulates miR-205 levels and vice versa, a feed-forward mechanism likely drives ExEn formation, after which miR-205 is without observed effects in mature ExEn cells. Unlike the vast majority of microRNAs, inactivation of miR-205 results in early embryonic lethality (38), whereas physiological up-regulation of miR-205 might compensate for Arf loss in the embryo proper.…”

Section: Discussionmentioning

confidence: 99%

Arf tumor suppressor and miR-205 regulate cell adhesion and formation of extraembryonic endoderm from pluripotent stem cells

Finkelstein

Sherr

2013

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

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Significance The Arf tumor suppressor gene is not expressed in most normal tissues but when activated by oncogenic stress signals engages a p53-dependent transcriptional program that prevents tumor formation. Surprisingly, expression of the p19 Arf protein in mouse embryoid bodies is required for the timely formation of extraembryonic endoderm (ExEn). Inactivation of Arf down-regulates a single microRNA, miR-205, which can “rescue” ExEn formation in Arf -null embryonic or induced pluripotent stem cells. During ExEn formation, miR-205 regulates a suite of genes that govern cell migration and adhesion, suggesting a conceptual basis for linking the roles of Arf in ExEn differentiation and tumor metastasis.

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“…By contrast, the deletion of many individual miRNAs seems to cause no or only subtle defects at the level of the whole organism (Chen et al, 2014;Kloosterman et al, 2007;Miska et al, 2007;Park et al, 2012). Three possible explanations for this discrepancy have been put forward and experimentally explored.…”

Section: Introductionmentioning

confidence: 99%

A framework for understanding the roles of miRNAs in animal development

2017

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MicroRNAs (miRNAs) contribute to the progressive changes in gene expression that occur during development. The combined loss of all miRNAs results in embryonic lethality in all animals analyzed, illustrating the crucial role that miRNAs play collectively. However, although the loss of some individual miRNAs also results in severe developmental defects, the roles of many other miRNAs have been challenging to uncover. This has been mostly attributed to their proposed function as tuners of gene expression or providers of robustness. Here, we present a view of miRNAs in the context of development as a hierarchical and canalized series of gene regulatory networks. In this scheme, only a fraction of embryonic miRNAs act at the top of this hierarchy, with their loss resulting in broad developmental defects, whereas most other miRNAs are expressed with high cellular specificity and play roles at the periphery of development, affecting the terminal features of specialized cells. This view could help to shed new light on our understanding of miRNA function in development, disease and evolution.

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A Resource for the Conditional Ablation of microRNAs in the Mouse

Cited by 165 publications

References 33 publications

The complexity of miRNA-mediated repression

The complexity of miRNA-mediated repression

Arf tumor suppressor and miR-205 regulate cell adhesion and formation of extraembryonic endoderm from pluripotent stem cells

A framework for understanding the roles of miRNAs in animal development

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