Journal of Analytical & Pharmaceutical Research New Player of ncRNAs: Long Non-coding RNAs Abstract Mini Review Long non-coding RNAs (lncRNAs) play important roles in a wide range of biological processes as regulatory factors at the epigenetic, transcriptional and Volume 3 Issue 4 - 2016 of lncRNAs discoveries including their identification, classifications and functions. post- transcriptional levels. In this review, we summarized the current knowledge 1Department of Biotechnology, Istanbul University, Turkey Keywords: Long non-coding RNAs; Discovery of lncRNAs; Classification of 2Department of Molecular Biology and Genetics, Istanbul University, Turkey lncRNAs; Post- transcriptional levels; Epigenetic; Regulatory factors *Corresponding author: Nermin Gözükırmızi, Department of MolecularBiology and Genetics, Istanbul University, Faculty of Science, Istanbul, 34118 Vezneciler, Turkey, Email: Received: | Published: November 04, 2016 November 15, 2016 Introduction Novel lncRNAs can be detected and discovered by both The mechanism underlying the functions of non-protein coding RNAs (ncRNAs or npcRNAs) that have no or little protein-coding experimental (next generation sequencing, NGS, technologies) potential is a fascinating area of research [1]. Based on transcript microarrays.and computational Then, thescreenings transcripts [33-35]. sequences First, are the mapped fragments to the of transcripts are obtained by using NGS technologies or tilling The criteria for discriminating between coding and non-coding length, ncRNAs are classified as short (<200 nt) and long ncRNAs as cDNA/EST in silico mining, whole-genome tilling array and sequencesreference genome of RNAs and are identified based on transcribed similarity unitsto known of the codingRNAs. (lncRNAs; >200 nt). The recent high-throughput analysis such RNA-sequencing (RNA-seq) has revealed that the transcription sequences or statistics of codon frequencies for coding potential landscape in eukaryotes is much more complex than had been to[36]. determine Typically, homologous BLASTX is mostdomains commonly in protein used data tool to for eliminate known expected [2-4]. Transcriptome analysis estimates transcripts sequence similarity detection [37]. Alternatively, HMMER3 help cover 90% of eukaryotic genome [5]. These approaches have npcRNAs) in many organisms, such as humans, animals, and is much more alternative tools for evaluating coding potential. plantsfacilitated [6-9]. the identification of thousands of novel ncRNAs (or transcripts with protein-coding potential [38]. However, there The most used tools are CPC (Cording-Potential Calculator) [39] by RNALncRNAs polymerase are arbitrarily II or III, defined and additionally, as RNA transcripts by polymerase that contain IV/V and PORTRAIT [40] use pair wise comparisons; in contrast, >200 nt but lack protein coding-potential which are transcribed PhyloCSF [41] and RNAcode [42] use multiple alignments. polyadenylation or non-polyadenylation, and can be located in the theseAnother computational popular approach, approaches, Coding experimental Potential Assessment methods such Tool, as nucleusin plants or [10-12]. cytoplasm. They The are researches processed have by splicing revealed or that nonsplicing, lncRNAs also uses an alignment-free logistic regression model [43]. Except may represent alternatively spliced forms of known genes [13], coding capacity of lncRNAs based on the periodicity of ribosome ribosomal profiling have been utilized to compute the protein products of antisense RNAs [14-17], double stranded RNAs [18], occupancy along the short translated ORFs [44]. by genome-wide approach which used gene expression data retained introns [13,19], short open reading frame [1,20,21]. RNA andAbout the presence1600 novel of chromatinmouse lncRNAs marks forhave promoter been identified regions polymerase III-derived RNAs [22] and RNA decoys mimicking miRNA targets [23]. Discovery of lncRNAs have been used to generate the human long intervening non- [8]. Combination of chromatin marks and RNA-seq data sets were discovered by using traditional gene mapping approaches In 1990s, H19 and Xist (X-inactive specific transcript) lncRNAs coding (lincRNA) catalog which comprise 8000 lincRNAs from 24 different human cell types and tissues [45]. More than discovered[24-16]. In bythe using later tilling years, arrays HOTAIR in the (HOX homeobox antisense gene intergenic regions 13,500 human lncRNAs have been annotated by GENCODE RNA) and HOTTIP (HOXA transcript at the distal tip) were and also, datasets from the 1000 Genomes Project have been utilized to reveal the association between lncRNAs and prostate then,(HOX thousandsclusters) [27,28]. of lncRNAs Using have genome-wide been determined approach, using 1600 similar novel cancer [30,46]. Cunnington et al. have reported the association mouse lncRNAs have been identified by Guttman et al. [8]. Since between 56 lncRNAs and disease related to traits ranging from diabetes to multiple sclerosis, Alzheimer’s disease, etc [47]. Both genome-wide approaches in human, mouse and plants [29-32]. computational and experimental analyses have shown that 125 Submit Manuscript | http://medcraveonline.com J Anal Pharm Res 2016, 3(4): 00064 Copyright: New Player of ncRNAs: Long Non-coding RNAs ©2016 ElifKarlik et al. 2/4 enhancer lncRNAs. Bidirectional lncRNAs, which are tending and can be induced by powdery mildew infection and heat stress to be highly conservative, are expressed within 1 kb of putative stress responsive lncRNAs in wheat were tissue-specific promoters in the opposite direction from the neighboring anthers,[48]. In addition, pistils, seeds, Zhang and et shoots al. [15] and systematically combining with identified the analysis 2224 bidirectional lncRNAs are associated with transcriptional lncRNAs by performing strand-specific RNA sequencing of rice regulatoryprotein-coding genes gene implicated [58,59]. Severalin cell studiesdifferentiation showed thatand Classificationof other available riceof lncRNAs RNA-seq datasets [32]. regionsdevelopment of the [60]. genome Enhancer and maylncRNA contribute (elncRNA to orenhancer eRNA), which are generally <2 kb, is transcribed from enhancer as transcript length, sequence and structure conservation, genomiclncRNAs location, are classifiedfunctions exertedbased on on DNAseveral or RNA,properties functioning such in chromatin looping and long-range gene activation, playing function [59]. eRNAs have been found to exert their functions mechanisms, and targeting mechanisms, association with an important role in system development and the formation annotated protein coding genes or repeats or biochemical Conclusionof homeostasis [61,62]. pathway or stability or subcellular structures [49,50]. Besides LncRNAs play important roles in a numerous biological lots of criteria for lncRNA classification, the most commonly used attributes are their size, localization and function. Typically, the have indicated that they are effective cis- and transregulators threshold value is 200 bases for length discrimination of ncRNAs. ofprocesses gene transcription, as regulatory and factors. also Functionalact as scaffolds analyses for ofchromatin- lncRNAs discrimination,Fewer than 200 genomic bases are locations considered of lncRNAs as small are ncRNAs also popular and more for modifying complexes. Nowadays, lncRNAs are considered as than 200 bases are classified as long ncRNAs [51]. After length size including cell differentiation and development, chromosome classifying. According to GENCODE for their genomic locations, dosagemajor regulatorscompensation, involved cell cyclein numerous control andcellular adaptation processes, to lncRNAsI. Antisense are classified lncRNAs, into which five aregroups: transcribed from the antisense strand, intersect any exon of a protein-coding locus on the association between salinity stress metabolism and barley the opposite strand, or published evidence of antisense environmental changes [63-65]. Our group has been investigating regulation of a coding gene. Their transcription was found to is likely to provide new insight into the complicated gene regulatorylncRNAs (unpublished network involving data). lncRNAs,Identification provide of novelnovel diagnostic lncRNAs response. It is considered that antisense lncRNAs, which opportunities, and pinpoint novel therapeutically targets. involvebe overlap genome genes imprinting, related to regulation condition ofspecific alternative or the splicing stress and translation, exert their function as on-off switch for these Acknowledgement II. genesSense [52-54].lncRNAs are trancribed from sense strand of protein- coding genes that overlapping transcripts contain a coding Dr. Nermin Gözükırmızı is proffessor at Molecular Biology gene within an intron on the same strand. and Genetics Department, Science Faculty of Istanbul University, Turkey. She received her Dr. rer. nat. Degree on Botany-Genetics at III. Intronic transcripts reside within introns of a coding gene, focuses on plant stress metabolism, transposons and epigenetics marks.Istanbul University, Turkey in 1979. Her current research interest sense intronic lncRNAs. Differential expression studies demonstratedwhich do not thathave expression exon-exon levels overlapping, of intronic is lncRNAs defined and as their biological variation during a physiological time course, M. Sc. Elif Karlık is PhD candidate at Biotechnology Department, or among different individuals of the same strain are tightly Institution of Science of Istanbul University,