Potential of Large Non-coding RNA (lncRNA) in Plants and Human Specially Neurogenerative and Cancer
Introduction With the discovery of the structure of DNA by Watson and Crick in 1953, there comes the discovery of the Central Dogma which states that genetic information stored in DNA is transcribed to messenger RNA (mRNA), followed by the formation of protein. . Further research has found the discovery of non-coding RNAs in the period 1950 to 1980s, the non-coding tRNA and rRNA in 1960 , followed by early regulatory non-coding RNA(ncRNA) in 1980 . The publication of Human Genomes in 2001, high – throughput sequencing and the ENCODE project have significantly boosted this research, leading to the characterisation of many ncRNAS. In this way, several ncRNAs have been known, such as micro RNAs (miRNAs), small interfering RNAs (siRNAs), small nuclear RNAs (sn RNAs), small nucleolar RNAs (snoRNAs), small Cajal body-specific RNA (scaRNA), piwi-interacting interacting RNA (piRNA) and Long non-coding RNAs (incRNAs). This scaRNA is a class of small non-coding RNA located in the Cajal body (membrane-less nuclear organelles found in eukaryotic cells ), crucial for small nuclear riboprotein (snRNP) biogenesis. Their functions are to guide the modification of of spliceosomal RNAs (U1, U2, U4, U5 and U12) for the proper functioning of the spliceosome during RNA processing. The piwi- interacting RNAs are small non-coding RNAs of generally 25-33 nucleotides long found in animal cells to form RNA-protein complexes with PIWI- like proteins to silence transposable elements from moving within the genome. PIWI proteins are a family of Argonaute proteins that interact with pi RNA to regulate gene expression. Different types of non-coding RNAs found in different organisms have a great potential in understanding the complexity of the organism and the regulatory functions of these RNAs in many cellular processes, particularly in gene regulation. With the advancement of transcriptome analysis in mammals large number of long transcripts have been know which have no protein-coding capacity and so it is called Long or Large non-coding RNAs (lncRNAs), the potential of which will be discussed below. Large/Long Non-coding RNA (lncRNA) and its Function With the advancement of transcriptome analysis in many organisms, it has been noted that the genomes of mammals and other organisms have produced thousands of long transcripts without any protein-coding capacity . These are called long non-coding RNAs (lncRNAs). It has been noted that about 70% of the mammalian genome is actively transcribed, but only 1-2% of it are protein –coding genes [1]. Large non-coding RNAs (lncRNAs) are generally of more than 200 nucleotides long without any protein-coding capacity but it has been noted that they have functions in gene regulation and disease development. With respect to protein-coding genes , lncRNAs can be intergenic, can be intergenic, antisense or intronic. They are also derived from pseudogenes. About 10,000 pseudogenes were found in the mouse and about 15,000 were identified in the human genome [2, 3]. Pseudogenes are non-functional copies of genes that have lost their protein-coding capacity due to mutations during evolution. They are derived from functional genes and are located near their parent genes. Pseudogenes have similarities with functional genes and they can produce non-coding RNAs on occasion . The mammalian pseudogene Lethe is known as large non- coding RNA (LncRNA) that plays a role in regulating the inflammatory stimuli and can be used as anti-inflammatory therapeutic suggesting the regulatory functions within the genome. But not all pseudogenes are functional but some have regulatory functions. The pseudogene Lethe can inhibit the ability of RelA protein (p65) , encoded from RELA gene, by binding to NF-kB promoters leading to RelA deficiency which can cause chronic muco-cutaneous lesions and susceptibility to TNF-induced apoptosis. lncRNAs can originate from various genomic processes like duplication of protein-coding genes , existing non-coding genes and through retrotransposition, tandem duplications and the insertion of transposable elements. lncRNAs may also originate from nuclear RNA polymerases through transcription and post transcriptional modifications . Five RNA polymerases , such as POL I, POL II, POL III and plant specific POL IV and POL V are transcribing diverse types of lncRNAs involving RNA-directed methylation as well as regulating transposable elements in plants [4]. On the basis of genomic localisation , lncRNAs are classified into three types such as i) Long intergenic non-coding RNAs without any overlapping with other gene ; ii) Intronic Large non-coding RNAs which is localised within the intron of a gene ; and iii) antisense lncRNA which is transcribed from the opposite DNA strand of the protein coding gene. Again some of the lncRNAs of mammals are derived from RNA polymerase II, for this reason those lncRNAs are similar to mRNA (1). There is another functional lncRNA known as XIst that helps in the inactivationof one of the X chromosomes of mammals. Dr. Maite Huarte, a molecular biologist at the University of Navarra in Pamplona, Spain, established the functional importance of lncRNA in cellular pathways and the regulatory functions in gene expression and also in different diseases of human, including cancer. It has been known that Transposable elements (TE) is responsible for providing new transcripts but they have another function of bringing functional elements into lncRNA. During the study of Genomic evolution, it has been noted that 45% to 65% of the genome originated from the parasite genome through the insertion of transposable elements. It has been observed that most of the lncRNAs contain at least one TE and human Endogenous Retrovirus (ERV) . The function of Xist ( X chromosome inactivation) and dosage compensation in mammals, is due to the presence of lncRNA. The sequence study of the Xist region showed that there are several repeat domains, like i) Rep-A originated through insertion of ERVB5; ii) Rep-C and Rep-F from ERVB 4 ; and iii) insertion of transposon. Another interesting finding is that the the number of lncRNA has increased during animal evolution, leading to the idea that there is a role of lncRNA in forming complexity in higher organisms [1]. Function of lncRNA Large ncRNAs have a diverse function in cellular processes like cell proliferation, differentiation, stress responses and apoptosis. … Read more