Emerging roles of long noncoding RNAs in neurological diseases and metabolic disorders

Editorial

07 November 2014

Out of darkness: long non-coding RNAs come of age

Yingqun Huang

Romano Regazzi

and

William C. Cho

4,710 views

0 citations

Editors

Yingqun Huang

School of Medicine, Yale University

Romano Regazzi

Université de Lausanne

William C Cho

Queen Elizabeth Hospital (QEH)

Impact

Potential roles of lncRNA in pancreatic islet development and endocrine cell function. Majority of lncRNAs are localized in the nucleus and participate in transcriptional and epigenetic regulation, acting as scaffolds of transcription and chromatin-modifying factors, or as transcriptional enhancers. (A) Regardless of species, different lncRNAs may influence the cell-fate and maturation of the various endocrine cell types. However, the cytoarchitectural differences, i.e., islet cellular composition, proportion, organization, innervations and vascularization patterns, between mouse and human islets may be partly determined by species-specific lncRNAs such as the large cluster of primate-specific (ps)-lncRNAs discovered in human cells. (B) The role of lncRNAs in endocrine islet cell functions, here represented by the components of canonical stimulus-secretion coupling in mouse (left) and human (right) beta cells, may also be in the level of transcriptional and epigenetic regulation of factors involved in cell-type specific functions. Considerable differences in nutrient sensing, metabolism, exocytotic events and electrophysiological properties between human and mouse beta cells may be a consequence of differential regulation of relevant genes, e.g., ion-channels and exocytotic proteins, by ps-lncRNAs.

Review

07 July 2014

Functional implications of long non-coding RNAs in the pancreatic islets of Langerhans

Jonathan L. S. Esguerra

and

Lena Eliasson

9,352 views

39 citations

Proposed model of imprinting at the DLK1–MEG3 locus: the DLK1–MEG3 imprinted region contains a primary ICR (IG-DMR) and secondary (MEG3–DMR) ICR that overlaps with the promoter of the MEG3. Both ICRs are paternally methylated. In mouse ES cells, the Meg3 lncRNA is believed to direct PRC2 mediated silencing of Dlk1 (Zhao et al., 2010).

Review

01 July 2014

The Missing lnc(RNA) between the pancreatic β-cell and diabetes

Vasumathi Kameswaran

and

Klaus H. Kaestner

14,710 views

50 citations

Review

01 July 2014

Roles of lncRNAs in pancreatic beta cell identity and diabetes susceptibility

Timothy J. Pullen

and

Guy A. Rutter

5,570 views

37 citations

Review

06 June 2014

Long non-coding RNA-dependent transcriptional regulation in neuronal development and disease

Brian S. Clark

and

Seth Blackshaw

Comprehensive analysis of the mammalian transcriptome has revealed that long non-coding RNAs (lncRNAs) may make up a large fraction of cellular transcripts. Recent years have seen a surge of studies aimed at functionally characterizing the role of lncRNAs in development and disease. In this review, we discuss new findings implicating lncRNAs in controlling development of the central nervous system (CNS). The evolution of the higher vertebrate brain has been accompanied by an increase in the levels and complexities of lncRNAs expressed within the developing nervous system. Although a limited number of CNS-expressed lncRNAs are now known to modulate the activity of proteins important for neuronal differentiation, the function of the vast majority of neuronal-expressed lncRNAs is still unknown. Topics of intense current interest include the mechanism by which CNS-expressed lncRNAs might function in epigenetic and transcriptional regulation during neuronal development, and how gain and loss of function of individual lncRNAs contribute to neurological diseases.

18,807 views

145 citations