Abstract
Of the diverse array of putative molecular and biological functions assigned to long non-coding RNAs (lncRNAs), one attractive perspective in epigenetic research has been the hypothesis that lncRNAs directly interact with the proteins involved in the modulation of chromatin conformation. Indeed, epigenetic modifiers are among the most frequent protein partners of lncRNAs that have been identified to date, of which histone methyltransferases and protein members of the Polycomb Repressive Complex PRC2 have received considerable attention. This review is focused on how lncRNAs interface with epigenetic factors to shape the outcomes of crucial biological processes such as regulation of gene transcription, modulation of nuclear architecture, X inactivation in females and pre-mRNA splicing. Because of our increasing knowledge of their role in development and cellular differentiation, more research is beginning to be done into the deregulation of lncRNAs in human disorders. Focusing on cancer, we describe some key examples of disease-focused lncRNA studies. This knowledge has significantly contributed to our ever-improving understanding of how lncRNAs interact with epigenetic factors of human disease, and has also provided a plethora of much-needed novel prognostic biomarker candidates or potential therapeutic targets. Finally, current limitations and perspectives on lncRNA research are discussed here.This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.
Highlights
While less than 2% of the human genome has protein-coding potential, over 70% of it can undergo transcription, meaning that most of the human transcriptome consists of non-coding RNA [1]
It has been found that Gomafu contains a repeat splicing-factor 1 (SF1)-binding motif that facilitates its direct binding to this SF [57], and that oligos mimicking the Gomafu SF1-binding site delayed the onset of splicing of a weak branch point [57]
In combination with hepatocellular carcinoma (HCC) patient data analysis linking high ZEB2-AS1 expression levels with worse progression-free survival, this study indicates its potential utility as an HCC prognosis biomarker [12]
Summary
While less than 2% of the human genome has protein-coding potential, over 70% of it can undergo transcription, meaning that most of the human transcriptome consists of non-coding RNA (ncRNA) [1]. The non-coding transcriptome can be conceptualized in terms of the varying sizes of noncoding transcripts, ranging from the shorter miRNAs and piRNAs of below 40 bp, through mid-sized snoRNAs (60 –300 bp) and enhancer RNAs (eRNA; 50–2000 bp) [2], to long non-coding RNAs (lncRNAs), a highly diverse group of transcripts that are all over 200 bp in length [3]. These can be further stratified into long intergenic ncRNA (lincRNAs), transcribed ultra-conserved regions (T-UCRs), natural antisense transcripts (NATs) and large intronic ncRNAs, among others. DNA looping and nuclear compartment formation, to involvement in alternative splicing and miRNA network cross-talk [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
