Long Non-Coding RNA Epigenetics.

Marek Kazimierczyk,Jan Wrzesinski

doi:10.3390/ijms22116166

Abstract

Long noncoding RNAs exceeding a length of 200 nucleotides play an important role in ensuring cell functions and proper organism development by interacting with cellular compounds such as miRNA, mRNA, DNA and proteins. However, there is an additional level of lncRNA regulation, called lncRNA epigenetics, in gene expression control. In this review, we describe the most common modified nucleosides found in lncRNA, 6-methyladenosine, 5-methylcytidine, pseudouridine and inosine. The biosynthetic pathways of these nucleosides modified by the writer, eraser and reader enzymes are important to understanding these processes. The characteristics of the individual methylases, pseudouridine synthases and adenine–inosine editing enzymes and the methods of lncRNA epigenetics for the detection of modified nucleosides, as well as the advantages and disadvantages of these methods, are discussed in detail. The final sections are devoted to the role of modifications in the most abundant lncRNAs and their functions in pathogenic processes.

Highlights

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Inosine (I) differs from adenine in that it possesses a carbonyl group instead of an amino group at position 6 of the purine ring. This modification only occurs in the doublestranded regions of mRNA, transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), and ncRNAs and is catalyzed by the writer protein, adenosine deaminase acting on RNA (ADAR)
Information available in the literature suggests that long noncoding RNAs (lncRNAs) epigenetics play a role in gene regulation through various mechanisms

Summary

General Remarks

Almost 80% of the human genome has been transcribed, only 2% of it (mRNA) codes proteins [1,2]. Members of the hnRNP family, including HNRNPA2B1 and HNRNPC, choose their target transcripts by screening the RNA binding motifs (RBMs), which are more accessible to them as a result of the m6A modification [85,86] This mechanism is known as the “RNA epigenetic m6A switch”, which means m6A alters the local structure of mRNA or lncRNA, to facilitate the binding of HNRNPs for biological regulation [87]. Inosine (I) differs from adenine in that it possesses a carbonyl group instead of an amino group at position 6 of the purine ring This modification only occurs in the doublestranded regions of mRNA, tRNA, rRNA, and ncRNAs and is catalyzed by the writer protein, adenosine deaminase acting on RNA (ADAR). Both edited and unedited lncRNAs can have different functions [115]

Detection of Modified Nucleotides

The Impact of lncRNA Epigenetics on lncRNA Function

Findings

Conclusions and Future Directions