Emerging role of non-coding RNA in health and disease

Abstract

Human diseases have always been a significant turf of concern since the origin of mankind. It is cardinal to know the cause, treatment, and cure for every disease condition. With the advent and advancement in technology, the molecular arena at the microscopic level to study the mechanism, progression, and therapy is more rational and authentic pave than a macroscopic approach. Non-coding RNAs (ncRNAs) have now emerged as indispensable players in the diagnosis, development, and therapeutics of every abnormality concerning physiology, pathology, genetics, epigenetics, oncology, and developmental diseases. This is a comprehensive attempt to collate all the existing and proven strategies, techniques, mechanisms of genetic disorders including Silver Russell Syndrome, Fascio- scapula humeral muscular dystrophy, cardiovascular diseases (atherosclerosis, cardiac fibrosis, hypertension, etc.), neurodegenerative diseases (Spino-cerebral ataxia type 7, Spino-cerebral ataxia type 8, Spinal muscular atrophy, Opitz-Kaveggia syndrome, etc.) cancers (cervix, breast, lung cancer, etc.), and infectious diseases (viral) studied so far. This article encompasses discovery, biogenesis, classification, and evolutionary prospects of the existence of this junk RNA along with the integrated networks involving chromatin remodelling, dosage compensation, genome imprinting, splicing regulation, post-translational regulation and proteomics. In conclusion, all the major human diseases are discussed with a facilitated technology transfer, advancements, loopholes, and tentative future research prospects have also been proposed.

Keywords: Cancer; Genetic diseases; Neurodegenerative and cardiovascular diseases.; Non‐coding RNA; lncRNA; miRNA.

Fig. 1

Timeline of molecular discoveries relating noncoding RNA

Fig. 2

Different Types of existing RNAs in living cells. RNA is either coding or non-coding. Housekeeping RNAs are fundamental and expressed primarily while regulatory noncoding RNAs are synthesised at specific phase of development or in response to some external stimuli. Various types of ncRNA include (1) lnc RNA (long non coding RNA 200nt, 5`cap and poly A tail) (2) ciRNA: circular intronic RNA (introns of protein coding genes) 3). circ RNA (circular RNA) head to tail splicing of exons. 4). eRNA (enhancer associated RNA) 5) siRNA (small interfering RNA)21-22nt. 6) piRNA (piwi interacting RNA) major role in transposon defence, germ cell development.7). miRNA (micro-RNA) 22-23nt highly conserved and plays role in post transcriptional gene silencing. 8) tRF (tRNA-derived RNA fragment) and tiRNA (tRNA-derived stress-induced RNAs) 9) YRNA functions during DNA replication in vertebrates and RNA stability. 10) TUCRNA (transcribed ultra-conserved RNAs) 11) Natural antisense transcripts (NAT) RNA 12) Telomeres RNA (TEL) is localized in clusters at the nuclear envelope. 13) ElciRNA retained intron circRNAs

Fig. 3

Biogenesis of noncoding RNA. Double stranded RNA are the major precursors which may be produced by inverted repeats in DNA, or two different RNA having complementary sequences may be simultaneously transcribed, or replication of double stranded RNA virus. Steps in biogenesis include (1) These may be formed in introns of pre-mRNA or miRNA genes having own promoters (transcribed by RNA polymerase II as large pri-miRNA hair pin loop like structure. This is recognised by DGCR8 (DiGeorge syndrome chromosomal region 8) and in association with Drosha forms Micro Processor Complex which cuts the RNA into smaller precursor microRNA. (2) This is then exported out of the nucleus into the cytoplasm with EXPORTIN-5 molecule. (3) In cytoplasm it is recognised by DICER helicase with RNase motif which cleaves the stem loop and releases microRNA molecule.4. Argonaute protein AGO-2 associates with miRNA/DICER, unwinds the double stranded RNA and releases one of the starnds. 5. It retains one of the strands known as Guide strand and other proteins now associate with it forming RISC (RNA Induced Silencing Complex) which guides this complex to the target complementary mRNA either by degrading mRNA or by inhibiting translation by preventing ribosomes from binding