Role of long non‐coding <scp>RNAs</scp> in the determination of β‐cell identity

Motterle, Anna; Sánchez-Parra, Clara; Regazzi, Romano

doi:10.1111/dom.12714

Cited by 22 publications

(12 citation statements)

References 137 publications

(176 reference statements)

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“…Interestingly, some LncRNAs are responsive to obesity. Motterle and coworkers reported that the expression of βlinc1 and βlinc2 correlated with body weight gain and glucose levels in diabetic animals, and the expression of the human ortholog of βlinc3 in the islets of T2D patients was altered and was related to the body mass index 14 . Also, our most recent work demonstrated that lncRNA Roit expression was downregulated in the islets of obese mice, impairing the transcription of the insulin gene and glucose homeostasis 15 .…”

Section: Introductionmentioning

confidence: 99%

The long non-coding RNA βFaar regulates islet β-cell function and survival during obesity in mice

et al. 2021

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Despite obesity being a predisposing factor for pancreatic β-cell dysfunction and loss, the mechanisms underlying its negative effect on insulin-secreting cells remain poorly understood. In this study, we identify an islet-enriched long non-coding RNA (lncRNA), which we name β-cell function and apoptosis regulator (βFaar). βFaar is dramatically downregulated in the islets of the obese mice, and a low level of βFaar is necessary for the development of obesity-associated β-cell dysfunction and apoptosis. Mechanistically, βFaar promote the synthesis and secretion of insulin by upregulating islet-specific genes Ins2, NeuroD1, and Creb1 through sponging miR-138-5p. In addition, using quantitative mass spectrometry, we identify TRAF3IP2 and SMURF1 as interacting proteins that are specifically associated with βFaar. We demonstrate that SMURF1 ubiquitin ligase activity is essential for TRAF3IP2 ubiquitination and activation of NF-κB-mediate β-cell apoptosis. Our experiments provide direct evidence that dysregulated βFaar contributes to the development of obesity-induced β-cell injury and apoptosis.

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Section: Introductionmentioning

confidence: 99%

The long non-coding RNA βFaar regulates islet β-cell function and survival during obesity in mice

et al. 2021

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“…Long non‐coding RNAs (lncRNAs) are emerging as important players in the regulation of β‐cell function . Some of these non‐coding transcripts may potentially also be released in exosomes.…”

Section: Metabolic Organs Releasing Exosomesmentioning

confidence: 92%

Exosomes as new players in metabolic organ cross‐talk

Guay

Regazzi

2017

Diabetes Obesity Metabolism

192

138

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Blood glucose homeostasis requires a constant communication between insulin-secreting and insulin-sensitive cells. A wide variety of circulating factors, including hormones, cytokines and chemokines work together to orchestrate the systemic response of metabolic organs to changes in the nutritional state. Failure in the coordination between these organs can lead to a rise in blood glucose levels and to the appearance of metabolic disorders such as diabetes mellitus. Exosomes are small extracellular vesicles (EVs) that are produced via the endosomal pathway and are released from the cells upon fusion of multivesicular bodies with the plasma membrane. There is emerging evidence indicating that these EVs play a central role in cell-to-cell communication. The interest in exosomes exploded when they were found to transport bioactive proteins, messenger RNA (mRNAs) and microRNA (miRNAs) that can be transferred in active form to adjacent cells or to distant organs. In this review, we will first outline the mechanisms governing the biogenesis, the cargo upload and the release of exosomes by donor cells as well as the uptake by recipient cells. We will then summarize the studies that support the novel concept that miRNAs and other exosomal cargo components are new important vehicles for metabolic organ cross-talk.cell-to-cell communication, diabetes, exosomes, metabolism, miRNAs | INTRODUCTIONIn modern societies, the combination of sedentary lifestyles with excessive caloric intake has resulted in a dramatic rise in the incidence of chronic metabolic diseases and in the associated premature deaths. Thus, it is becoming urgent to find novel strategies to cure or prevent the development of these diseases and to stop their epidemic progression. To achieve this goal, we need to improve our basic knowledge of the biological mechanisms governing the maintenance of glucose homeostasis.Several organs contribute to the regulation of blood glucose levels and the communication between them is vital to achieve this and were first thought to participate in the selective removal of unwanted cell components. However, the interest in these EVs exploded in the last decade, when they were found to transport bioactive molecules, including proteins and nucleic acids, which can be transferred in active form to recipient cells. 5,6 Exosomes are now seen as vehicles of a new cell-to-cell signalling pathway whose rules and limitations remain to be completely established. Also, a consensus is still lacking about the nomenclature and the most appropriate isolation method of exosomes and other types of microvesicles released by the cells. Typically, the term "exosome" is used to designate EVs with a diameters of 50 to 150 nm that originate from the The most common strategy used to isolate exosomes remains differential centrifugation. Therefore, unless specified, in this review we will focus mainly on studies on exosomes (also called exosome-like microvesicles or small EVs) that were isolated by high speed ultra-centrifugation. | Exosome biogenesis...

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“…Although the role of miRNAs in diabetes has been well established (9), analyses of lncRNAs in islets have lagged behind their short ncRNA counterparts. However, several recent studies provide evidence that lncRNAs are crucial components of the islet regulome and may have a role in diabetes (27). For example, a genome-wide association study examined T2D susceptibility loci within unknown genomic associations and found that a significant percentage (>16%) of T2D loci contained islet lncRNAs within 150 kb of the reported lead single nucleotide polymorphism (SNP) (28), suggesting lncRNAs are essential for normal pancreatic function.…”

Section: Noncoding Rnasmentioning

confidence: 99%

Islet Long Noncoding RNAs: A Playbook for Discovery and Characterization

Singer

Sussel

2018

Diabetes

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Diabetes is a complex group of metabolic disorders that can be accompanied by several comorbidities, including increased risk of early death. Decades of diabetes research have elucidated many genetic drivers of normal islet function and dysfunction; however, a lack of suitable treatment options suggests our knowledge about the disease remains incomplete. The establishment of long noncoding RNAs (lncRNAs), once dismissed as "junk" DNA, as essential gene regulators in many biological processes has redefined the central role for RNA in cells. Studies showing that misregulation of lncRNAs can lead to disease have contributed to the emergence of lncRNAs as attractive candidates for drug targeting. These findings underscore the need to reexamine islet biology in the context of a regulatory role for RNA. This review will ) highlight what is known about lncRNAs in the context of diabetes,) summarize the strategies used in lncRNA discovery pipelines, and ) discuss future directions and the potential impact of studying the role of lncRNAs in diabetes.

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Role of long non‐coding RNAs in the determination of β‐cell identity

Cited by 22 publications

References 137 publications

The long non-coding RNA βFaar regulates islet β-cell function and survival during obesity in mice

The long non-coding RNA βFaar regulates islet β-cell function and survival during obesity in mice

Exosomes as new players in metabolic organ cross‐talk

Islet Long Noncoding RNAs: A Playbook for Discovery and Characterization

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