The Role of 3'UTR of RNA Viruses on mRNA Stability and Translation Enhancement

Abstract

: The central dogma of molecular biology explains the flow of genetic information from DNA to functional products such as proteins. In most cases, a linear relationship with high correlation coefficient exists between the concentration of mRNA, the middle man, and the functional product. Untranslated regions (UTRs) of RNA form considerable base pairing that contributes to the secondary and tertiary structures of mRNA. The interaction between the mRNA secondary structures (cis-elements), RNA-binding proteins (RBP) and miRs (trans-element) are critical determinants of mRNAs' fate and stability. Among different viral families, the positive sense (+) RNA viruses use the simplest possible strategy of replication and expression; as the same molecule functions both as a genome and mRNA. Additionally, nucleotide composition and codon usage of +RNA viruses are the closest to human codon adaptation index (CAI). Since the origin of replication of viral intermediate RNA molecules is at the 3'-end of the genome, the 3'UTR plays a role in viral RNA replication. Moreover, the messenger role of RNA likely places functional demands on the 3'UTR to serve a role typical of cellular mRNA. This article reviews the effect of 3'UTR of RNA viruses with positive sense and genomes on mRNA stability and translation improvement. A range of animal (e.g., Dengue, Sindbis, Corona and Polio) and plant (Barley yellow dwarf, Brome mosaic, Turnip crinkle, Tobacco mosaic, Cowpea mosaic and Alfalfa mosaic) viruses are examined to highlight the role of 3'UTR in viral survival and as a potential target for pharmaceutical applications.

A Novel Lineage of Cile-Like Viruses Discloses the Phylogenetic Continuum Across the Family Kitaviridae

“…In SvRSV isolates, these regions were more similar (98% nt sequence identity) than in LigLV and LigCSV (83–88% nt sequence identity). When the 3′-termini of the cileviruses CiLV-C, CiLV-C2, and PfGSV were included in the alignment, the presence of highly conserved nucleotide sequences in all these viruses became evident, likely denoting the putative functional role of these sequences as described in other viruses ( Dreher, 1999 ; Liu et al, 2020 ; Rasekhian et al, 2021 ). The implementation of the UTR-backed iterative BLASTN approach ( Zhang et al, 2022 ) using the 3′-terminus conserved nucleotide sequences of SvRSV, LigCSV, and LigLV, resulted in the recovery of contigs corresponding to the RNA1 and RNA2 segments already known, and new putative genomic segments were not identified.…”

mRNA therapeutics for disease therapy: principles, delivery, and clinical translation

“…36,37 Therefore, constructing a highly structured 3 0 UTR is a common optimization method for mRNA sequences. [38][39][40] In addition, the researchers discovered a surprising rule for mRNA sequence design: the more efficient the translation, the more unstable the mRNA. 41 In other words, there is a mutual constraint between the increase of polyribosome loading on mRNA molecules and the maximization of total target protein production in a certain time, so the mRNA structure needs to be adjusted to achieve a balance between translation efficiency and stability to design the mRNA structure.…”

Application of Modified mRNA in Somatic Reprogramming to Pluripotency and Directed Conversion of Cell Fate

“…UTRs may influence translation efficiency due to the competition of other proteins with ribosomes for binding to mRNA [ 26 ]. 3′ UTR functions as the cytoplasmic localization of mRNA, which contains sequences that allow RNA transcript to go to the translated region [ 27 , 28 ]. The open reading frame is a coding region, which is decoded and translated into proteins by ribosomes.…”