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Viral Decay Acceleration: 

Pathway to Viral Eradication 

mRNA degradation is an essential process for regulating gene expression in eukaryotic cells. Eukaryotic mRNA molecules are composed of a 5′ cap, a 5′ untranslated region (UTR), a coding sequence (CDS), a 3′ untranslated region (UTR), and a 3′ poly(A) tail. During translation, the mRNA is recognized by initiation factors, such as eIF4E and PABPC1. The 5′ cap is bound by eIF4E, and the poly(A) tail is bound by PABPC1. These interactions stabilize the mRNA and facilitate translation by promoting the formation of a closed-loop structure with eIF4G. This structure protects the mRNA from degradation.

Overview of mRNA Degradation Pathways


Process of mRNA Degradation

The first step in mRNA degradation is the removal of the 3′ poly(A) tail. This process is mediated by deadenylases, such as the CCR4-NOT and PAN2-PAN3 complexes. PAN2-PAN3 removes longer poly(A) tails, while CCR4-NOT trims shorter tails. After deadenylation, the 5′ cap is removed by the decapping complex DCP1/2. The mRNA is then degraded by exonucleases: the 5′-3′ exonuclease Xrn1 and the 3′-5′ exonuclease exosome complex. These enzymes degrade the mRNA from the exposed ends.

Nonsense-Mediated Decay (NMD)

Besides exonucleolytic decay, mRNA can also undergo internal cleavage, known as endonucleolytic decay. This process is part of the mRNA surveillance mechanism called nonsense-mediated decay (NMD), which targets mRNAs with premature stop codons (PTCs). NMD leads to the decapping of the mRNA and degradation by Xrn1. Under certain stress conditions, such as viral infection or hypoxia, NMD is suppressed.


RNA Granules: P-bodies and Stress Granules

mRNA degradation typically occurs in specialized cytoplasmic structures known as RNA granules. P-bodies contain enzymes such as DCP1/2, Xrn1, and CCR4-NOT, which regulate mRNA decay. Stress granules (SGs), which form in response to cellular stress, contain untranslated mRNA and translation initiation factors. These granules play an important role in regulating mRNA stability and translation. Both P-bodies and SGs are dynamic structures that exchange components and help control mRNA turnover.

Virus Interaction with mRNA Degradation Pathways

Viruses often manipulate host cell machinery to avoid mRNA degradation and promote their own replication. For example, flaviviruses, including West Nile virus (WNV) and dengue virus (DV), inhibit stress granule formation by interfering with SG components. Hepatitis C virus (HCV) reduces P-body numbers and repositions P-body components to viral replication sites. These viral strategies help ensure efficient replication and evade cellular defense mechanisms that normally target viral mRNA for degradation.



Exploring VDA: Impact on Viral Fitness & Mutagenic Selectivity

RNA as an Organic Code

Nucleic acids, proteins, and lipids form biological codes that are fundamental to life. The study of RNA dates back to the late 1800s when it was differentiated from DNA. In the 1950s, key discoveries revealed the double-helix structure of DNA, which led to a deeper understanding of genetic information storage and transfer. RNA is structurally similar to DNA but has different roles, particularly in gene regulation and expression.


RNA’s Functions Through Its Complex Structure

RNA plays a central role in transcription, splicing, localization, translation, and decay. Its structure directly affects its interaction with RNA-binding proteins, influencing gene regulation. RNA structure varies among cells and provides insight into cell identity and differentiation. Unlike gene expression profiles, RNA structure profiles can better distinguish between cell types. New methods like single-cell structure probing (sc-SPORT) allow for the study of RNA structures at the single-cell level, revealing important information about RNA's functions in health and disease.


RNA Structure at Various Levels

RNA structure can be analyzed at multiple levels:

​Primary structure:

 The linear sequence of nucleotides.

Secondary structure:

 The base-pairing patterns that form loops, stems, and bulges.                                                                                      



​Tertiary structure:

Higher-order folding and interactions that give RNA its three-dimensional shape.

Quaternary and Quinary structures:

 Complex formations that involve interactions between multiple RNA molecules or other biomolecules.

=> These structures are essential for RNA's diverse functions in gene expression and regulation. RNA's ability to change its conformation in response to its environment or interactions with proteins and other molecules adds to its versatility and importance in cellular processes.