Abstract

Differential expression of long non-coding RNAs (lncRNAs) during differentiation and their misregulation in cancer highlight their potential as cell fate regulators. While some example lncRNAs have been characterized in great detail, the functional in vivo relevance of others has been called into question. Finding functional lncRNAs will most probably require a combination of complementary approaches that will greatly vary depending on their mode of action. In this review, we discuss the different tools available to dissect genetically lncRNA requirements and how each is best suited to studies in particular contexts. Moreover, we review different strategies used to select candidate lncRNAs and give an overview of lncRNAs described to regulate development and cancer through different mechanisms.

Highlights

  • Regulated gene expression is the basis for the extensive variety of cell types our bodies generate from the same set of DNA instructions

  • The ever-expanding catalogue of long non-coding RNAs (lncRNAs) first became apparent from efforts to annotate the functional features of the human genome, which showed that the vast majority of the genome was transcribed [5]

  • Concluding remarks lncRNAs are being heavily studied in the context of development and cancer, as their unique properties could allow them to interact with multiple proteins via three-dimensional structures and recognize other nucleic acids by base pairing

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Summary

Introduction

Regulated gene expression is the basis for the extensive variety of cell types our bodies generate from the same set of DNA instructions. Thousands of long non-coding RNAs (lncRNAs) are expressed in a cell-typespecific manner during differentiation and in certain cancers. This has been extensively reported in many organisms and cell types [1,2,3,4], yet demonstrating that these molecules play functional roles has not been easy. Biochemical partners have been carefully identified, yet in vivo evidence for their function is missing or questions have been raised regarding the relevance of the previously reported mechanisms of action [20,21] Bridging this gap is essential for building a solid body of knowledge of how lncRNAs function in cell fate choices and the mechanisms by which they act. License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited

Cell-type-specific expression of long non-coding RNAs: cause or consequence?
Long non-coding RNA expression during development
Long non-coding RNA misregulation in cancer
Finding functional long non-coding RNAs
Different tools for different questions
Which long non-coding RNAs to study
Long non-coding RNAs shape development and cancer
Effects on chromatin and DNA interactions
Effects on mRNA stability and processing
Effects on protein stability and function
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58. Li L et al 2013 Targeted disruption of hotair
65. Konermann S et al 2014 Genome-scale
68. Kretz M et al 2013 Control of somatic
75. Matsumoto A et al 2016 mTORC1 and muscle

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