The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer

Abstract

Most of our transcribed RNAs are represented by non-coding sequences. Long non-coding RNAs (lncRNAs) are transcripts with no or very limited protein coding ability and a length >200nt. They can be epigenetically modified. N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G) and 2’-O-methylation (Nm) are some of the lncRNAs epigenetic modifications. The epigenetic modifications of RNA are controlled by three classes of enzymes, each playing a role in a specific phase of the modification. These enzymes are defined as “writers”, “readers” and “erasers”. m6A and m5C are the most studied epigenetic modifications in RNA. These modifications alter the structure and properties, thus modulating the functions and interactions of lncRNAs. The aberrant expression of several lncRNAs is linked to the development of a variety of cancers and the epigenetic signatures of m6A- or m5C-related lncRNAs are increasingly recognized as potential biomarkers of prognosis, predictors of disease stage and overall survival. In the present manuscript, the most up to date literature is reviewed with the focus on m6A and m5C modifications of lncRNAs and their significance in cancer.