The Functions of MicroRNAs: mRNA Decay and Translational Repression

Iwakawa, Hiro-oki; Tomari, Yukihide

doi:10.1016/j.tcb.2015.07.011

Cited by 643 publications

(489 citation statements)

References 145 publications

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“…In recent years, the discovery of the highly conserved enzymes that produce mature miRNAs -Drosha and Dicer (Bernstein et al, 2001;Hutvagner et al, 2001;Lee et al, 2003) -has enabled the collective function of canonical miRNAs to be probed in various model organisms. Moreover, mature miRNAs exert their repressive function in association with a member of the Argonaute (Ago) protein family (reviewed by Iwakawa and Tomari, 2015), and the removal of this Ago effector protein has also been a useful tool for assessing the contribution of miRNA-mediated repression to different processes. For instance, in Caenorhabditis elegans, zygotic removal of both miRNA-dedicated Argonautes, ALG-1 and ALG-2, causes embryonic arrest during morphogenesis (Vasquez-Rifo et al, 2012).…”

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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Section: Introductionmentioning

confidence: 99%

A framework for understanding the roles of miRNAs in animal development

2017

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“…miRNAs can be encoded by specific miRNA genes, as well as by introns of protein-coding genes through independent promoters (5), and often modulate the same biological mechanisms as the protein encoded by the host gene (73). miRNAs regulate gene expression through mRNA decay and translational repression (28). They are incorporated into an RNA-induced silencing complex with Argonaute proteins that have RNase H activity (28) and can cleave interacting mRNA targets following imperfect base pairing (61).…”

mentioning

confidence: 99%

“…miRNAs regulate gene expression through mRNA decay and translational repression (28). They are incorporated into an RNA-induced silencing complex with Argonaute proteins that have RNase H activity (28) and can cleave interacting mRNA targets following imperfect base pairing (61).…”

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confidence: 99%

Biological roles of microRNAs in the control of insulin secretion and action

Caldérari

Diawara

Garaud

et al. 2017

Physiological Genomics

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microRNAs (miRNAs) are intracellular and circulating molecular components contributing to genome expression control through binding mRNA targets, which generally results in downregulated mRNA expression. One miRNA can target several mRNAs, and one transcript can be targeted by several miRNAs, resulting in complex fine-tuning of regulation of gene networks and signaling pathways. miRNAs regulate metabolism, adipocyte differentiation, pancreatic development, β-cell mass, insulin biosynthesis, secretion, and signaling, and their role in diabetes and obesity is emerging. Their pathophysiological effects are essentially dependent on cellular coexpression with their mRNA targets, which can show tissue-specific transcriptional responses to disease conditions and environmental challenges. Current knowledge of miRNA biology and their impact on the pathogenesis of diabetes and obesity is based on experimental data documenting miRNA expression generally in single tissue types that can be correlated with expression of target mRNAs to integrate miRNA in functional pathways and gene networks. Here we present results from the most significant studies dealing with miRNA function in liver, fat, skeletal muscle, and endocrine pancreas and their implication in diabetes and obesity

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“…However, this toolkit was adapted over evolutionary time to contribute to the regulation of eukaryotic protein synthesis. Both plant and animal genomes encode a variety of short RNA strands, typically referred to as micro RNA (miRNA), that are not destined for translation but as a secondary level of transcriptional control (Iwakawa and Tomari 2015). Pri-miRNA are produced in the nucleus, generally as hairpin structures present in mRNA introns.…”

Section: What Is Rna Interference?mentioning

confidence: 99%

RNA interference-based technology: what role in animal agriculture?

et al. 2017

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Abstract. Animal agriculture faces a broad array of challenges, ranging from disease threats to adverse environmental conditions, while attempting to increase productivity using fewer resources. RNA interference (RNAi) is a biological phenomenon with the potential to provide novel solutions to some of these challenges. Discovered just 20 years ago, the mechanisms underlying RNAi are now well described in plants and animals. Intracellular double-stranded RNA triggers a conserved response that leads to cleavage and degradation of complementary mRNA strands, thereby preventing production of the corresponding protein product. RNAi can be naturally induced by expression of endogenous microRNA, which are critical in the regulation of protein synthesis, providing a mechanism for rapid adaptation of physiological function. This endogenous pathway can be co-opted for targeted RNAi either through delivery of exogenous small interfering RNA (siRNA) into target cells or by transgenic expression of short hairpin RNA (shRNA). Potentially valuable RNAi targets for livestock include endogenous genes such as developmental regulators, transcripts involved in adaptations to new physiological states, immune response mediators, and also exogenous genes such as those encoded by viruses. RNAi approaches have shown promise in cell culture and rodent models as well as some livestock studies, but technical and market barriers still need to be addressed before commercial applications of RNAi in animal agriculture can be realised. Key challenges for exogenous delivery of siRNA include appropriate formulation for physical delivery, internal transport and eventual cellular uptake of the siRNA; additionally, rigorous safety and residue studies in target species will be necessary for siRNA delivery nanoparticles currently under evaluation. However, genomic incorporation of shRNA can overcome these issues, but optimal promoters to drive shRNA expression are needed, and genetic engineering may attract more resistance from consumers than the use of exogenous siRNA. Despite these hurdles, the convergence of greater understanding of RNAi mechanisms, detailed descriptions of regulatory processes in animal development and disease, and breakthroughs in synthetic chemistry and genome engineering has created exciting possibilities for using RNAi to enhance the sustainability of animal agriculture.

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The Functions of MicroRNAs: mRNA Decay and Translational Repression

Cited by 643 publications

References 145 publications

A framework for understanding the roles of miRNAs in animal development

A framework for understanding the roles of miRNAs in animal development

Biological roles of microRNAs in the control of insulin secretion and action

RNA interference-based technology: what role in animal agriculture?

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