From RNA sequence to its three-dimensional structure: geometrical structure, stability and dynamics of selected fragments of SARS-CoV-2 RNA.

In this computational study, we explore the folding of a particular sequence using various computational tools to produce two-dimensional structures, which are then transformed into three-dimensional structures. We then study the geometry, energetics and dynamics of these structures using full electron quantum-chemical and classical molecular dynamics calculations. Our study focuses on the SARS-CoV-2 RNA fragment GGaGGaGGuguugcaGG and its various structures, including a G-quadruplex and five different hairpins.

Genome sequence analysis suggests coevolution of the DIS, SD, and Psi hairpins in HIV-1 genomes.

HIV-1 RNA dimerization is a critical step in viral life cycle. It is a prerequisite for genome packaging and plays an important role in reverse transcription and recombination. Dimerization is promoted by the DIS (dimerization initiation site) hairpin located in the 5' leader of HIV-1 genome.

Structural transitions in poly(A), poly(C), poly(U), and poly(G) and their possible biological roles.

The homopolynucleotide (homo-oligonucleotide) tracts function as regulatory elements at various stages of mRNAs life cycle. Numerous cellular proteins specifically bind to these tracts. Among them are the different poly(A)-binding proteins, poly(C)-binding proteins, multifunctional fragile X mental retardation protein which binds specifically both to poly(G) and poly(U) and others.

Structural insight into HIV-1 reverse transcription initiation in MAL-like templates (CRF01_AE, subtype G and CRF02_AG).

Based on the known structural model for reverse transcription initiation complex of the human immunodeficiency virus type 1 (HIV-1) MAL isolate, we attempted to predict a structural behavior of MAL-like templates (CRF01_AE, subtype G and CRF02_AG) within the initiation complex by in silico experiments. Switches from the D-duplex (dimerization-competent) conformation to the I-duplex (initiation-competent) conformation and then to conformations with an open primer activation signal (PAS) structure have been examined for four fragments of U5 and primer binding site (PBS) region, the minimal fragment (nt 121-243), fragment 1 (nt 110-243), fragment 2 (nt 113-259), and extended fragment 2 (nt 109-261). Switches from the D-duplex conformation to the I-duplex conformation in the minimal fragment or fragment 1 and from the I-duplex conformation to conformations with exposed PAS motif in fragment 1 are similar in all MAL-like templates.

Structural model of the complete poly(A) region of HIV-1 pre-mRNA.

In the HIV-1 retrovirus, identical sequences encompassing the AAUAAA hexamer and the U/GU-rich downstream sequence element (DSE) that compose the core poly(A) site are present at both the 5' and 3' ends of the HIV-1 pre-mRNA. The AAUAAA hexamer is partly occluded by base pairing in the upper part of a semi-stable polyA hairpin. This sets the stage for regulation of HIV-1 polyadenylation, which involves reaction suppression at the 5' end and its stimulation at the 3' end.

Downstream elements of mammalian pre-mRNA polyadenylation signals: primary, secondary and higher-order structures.

Primary, secondary and higher-order structures of downstream elements of mammalian pre-mRNA polyadenylation signals [poly(A) signals] are re viewed. We have carried out a detailed analysis on our database of 244 human pre-mRNA poly(A) signals in order to characterize elements in their downstream regions. We suggest that the downstream region of the mammalian pre-mRNA poly(A) signal consists of various simple elements located at different distances from each other.

What nuclease cleaves pre-mRNA in the process of polyadenylation?

A transcript-specific cleavage by a large set of proteins is the first stage of eukaryotic pre-mRNA polyadenylation. The main participant of this reaction-endonuclease-has not been discovered until now. However, mammalian CPSF-30 and yeast Yth 1p proteins are known to be homologues to Drosophila Clipper (CLP) protein, which possesses endoribonucleolytic activity.

Structural transitions in polycytidylic acid: proton buffer capacity data.

The pH-dependences of proton buffer capacity of poly(C) were computed on the basis of the literature data. In these curves there were observed four peaks: two narrow and two wide ones. The first narrow peak reflects the process of cooperative formation of double helices, which is induced by protonation of the N3 atom of nucleotide bases.