The application of a new generation of sequencing techniques has revealed that most of the genome has already been transcribed. However, only a small part of the genome codes proteins. The rest of the genome "dark matter” belongs to divergent groups of non-coding RNA (ncRNA), that is not translated into proteins. There are two groups of ncRNAs, which include small and long non-coding RNAs (sncRNA and lncRNA respectively). Over the last decade, there has been an increased interest in lncRNAs and their interaction with cellular components. In this review, we presented the newest information about the human lncRNA interactome. The term lncRNA interactome refers to cellular biomolecules, such as nucleic acids, proteins, and peptides that interact with lncRNA. The lncRNA interactome was characterized in the last decade, however, understanding what role the biomolecules associated with lncRNA play and the nature of these interactions will allow us to better understand lncRNA's biological functions in the cell. We also describe a set of methods currently used for the detection of lncRNA interactome components and the analysis of their interactions. We think that such a holistic and integrated analysis of the lncRNA interactome will help to better understand its potential role in the development of organisms and cancers.

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.

Pseudouridine (Ψ), the most common single modified nucleoside in ribosomal RNA, has been positioned in the small subunit (SSU) and large subunit (LSU) RNAs of a number of representative species. Most of the information has been obtained by application of a rapid primed reverse transcriptase sequencing technique. The locations of these Ψ residues have been compared. Many sites for Ψ are the same among species, but others are distinct. In general, the percentage Ψ in multicellular eukaryotes is greater than in prokaryotes. In LSU RNA, the Ψ residues are strongly clustered in three domains, all of which are near or connected to the peptidyl transferase center. There is no apparent clustering of Ψ in SSU RNA. The Ψ sites in LSU RNA overlap those for the methylated nucleosides, but this is not the case in SSU RNA. There are 265 Ψ sites known to nucleotide resolution, of which 246 are in defined secondary structures, and 112 of these are in nonidentical structural contexts. All 246 Ψ sites can be classified into five structural types. Two Escherichia coli Ψ synthases have been cloned and characterized, one for Ψ516 in SSU RNA and one for Ψ746 in LSU RNA. The Ψ746 synthase recognizes free RNA, but the Ψ516 enzyme requires an intermediate RNP particle. Possible functional roles for Ψ in the ribosome are discussed.Key words: pseudouridine, sequencing, modified nucleosides, ribosomal RNA.