Abstract

In this review, we provide an overview of the current knowledge on the role of different classes of non-coding RNAs for islet and β-cell development, maturation and function. MicroRNAs (miRNAs), a prominent class of small RNAs, have been investigated for more than two decades and patterns of the roles of different miRNAs in pancreatic fetal development, islet and β-cell maturation and function are now emerging. Specific miRNAs are dynamically regulated throughout the period of pancreas development, during islet and β-cell differentiation as well as in the perinatal period, where a burst of β-cell replication takes place. The role of long non-coding RNAs (lncRNA) in islet and β-cells is less investigated than for miRNAs, but knowledge is increasing rapidly. The advent of ultra-deep RNA sequencing has enabled the identification of highly islet- or β-cell-selective lncRNA transcripts expressed at low levels. Their roles in islet cells are currently only characterized for a few of these lncRNAs, and these are often associated with β-cell super-enhancers and regulate neighboring gene activity. Moreover, ncRNAs present in imprinted regions are involved in pancreas development and β-cell function. Altogether, these observations support significant and important actions of ncRNAs in β-cell development and function.

Highlights

  • Introduction to Pancreas and Islet CellDevelopmentThe pancreas is a unique organ in our body consisting of two major compartments: The exocrine pancreas and the endocrine pancreas

  • Considering the cell-/tissue-specific nature of several non‐coding RNAs (ncRNAs) [58,168,169], it is very likely that the number of ncRNAs that make up the major classes would exceed the number of protein-coding genes that have been identified in the human genome

  • The discovery of ncRNAs that are directly linked to survival and function of insulin-producing cells will be critical in understanding their potential in predicting, preventing and/or reversing diabetes

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Summary

Introduction to Pancreas and Islet Cell Development

The pancreas is a unique organ in our body consisting of two major compartments: The exocrine pancreas and the endocrine pancreas. The Aub-piRISCs initiates along with the Ago to produce secondary piRNAs, which cycles a ping-pong piRNA characteristic feature of 1U/10A partners and a 10-nt 5 overlap These two effectors act complementary to cleave sense and antisense transposon transcripts through Slicer activities silencing transposons [43,44]. LncRNAs are in general distinguished as ncRNAs which are >200 nts long and characterized based on their location mostly encoded by intergenic regions (long intergenic/intervening (i) RNAs) and some overlapping the protein-coding genes [29,57]. In addition similar to circRNAs, lncRNAs alter protein translation (as well as degradation) for example through acting to sequester miRNAs from protein or mRNA targets [66,67]. The knockdown (KD) of PTENP1 leads to an increase in these microRNAs and decreased PTEN levels, resulting in increased cell proliferation [68]

MicroRNA Biogenesis and Function
Stage-Specific Expression of MicroRNAs
Pancreatic Islet Circular RNAs
NcRNAs in Pancreatic Alpha Cells versus β-Cells
Fetal Programming and ncRNAs in Control of β-Cell Growth and Exocytosis
Species Differences in ncRNAs between Mouse and Human
Findings
Discussion and Conclusions
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