RNA Structure: Past, Future, and Gene Therapy Applications.

First believed to be a simple intermediary between the information encoded in deoxyribonucleic acid and that functionally displayed in proteins, ribonucleic acid (RNA) is now known to have many functions through its abundance and intricate, ubiquitous, diverse, and dynamic structure. About 70-90% of the human genome is transcribed into protein-coding and noncoding RNAs as main determinants along with regulatory sequences of cellular to populational biological diversity. From the nucleotide sequence or primary structure, through Watson-Crick pairing self-folding or secondary structure, to compaction via longer distance Watson-Crick and non-Watson-Crick interactions or tertiary structure, and interactions with RNA or other biopolymers or quaternary structure, or with metabolites and biomolecules or quinary structure, RNA structure plays a critical role in RNA's lifecycle from transcription to decay and many cellular processes.

The RNA Revolution in the Central Molecular Biology Dogma Evolution.

Human genome projects in the 1990s identified about 20,000 protein-coding sequences. We are now in the RNA revolution, propelled by the realization that genes determine phenotype beyond the foundational central molecular biology dogma, stating that inherited linear pieces of DNA are transcribed to RNAs and translated into proteins. Crucially, over 95% of the genome, initially considered junk DNA between protein-coding genes, encodes essential, functionally diverse non-protein-coding RNAs, raising the gene count by at least one order of magnitude.

Potential Transcriptional Enhancers in Coronaviruses: From Infectious Bronchitis Virus to SARS-CoV-2.

Coronaviruses constitute a global threat to human and animal health. It is essential to investigate the long-distance RNA-RNA interactions that approximate remote regulatory elements in strategies, including genome circularization, discontinuous transcription, and transcriptional enhancers, aimed at the rapid replication of their large genomes, pathogenicity, and immune evasion. Based on the primary sequences and modeled RNA-RNA interactions of two experimentally defined coronaviral enhancers, we detected via an in silico primary and secondary structural analysis potential enhancers in various coronaviruses, from the phylogenetically ancient avian infectious bronchitis virus (IBV) to the recently emerged SARS-CoV-2.

Bioinformatics Insights on Viral Gene Expression Transactivation: From HIV-1 to SARS-CoV-2.

Viruses provide vital insights into gene expression control. Viral transactivators, with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to transacting responsive regions (TARs) in viral and host RNAs.

Intragenomic rearrangements involving 5'-untranslated region segments in SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses.

Background: Variation of the betacoronavirus SARS-CoV-2 has been the bane of COVID-19 control. Documented variation includes point mutations, deletions, insertions, and recombination among closely or distantly related coronaviruses. Here, we describe yet another aspect of genome variation by beta- and alphacoronaviruses that was first documented in an infectious isolate of the betacoronavirus SARS-CoV-2, obtained from 3 patients in Hong Kong that had a 5'-untranslated region segment at the end of the ORF6 gene that in its new location translated into an ORF6 protein with a predicted modified carboxyl terminus.

Interview: commercial translation of cell-based therapies and regenerative medicine: learning by experience. Interview by Emily Culme-Seymour.

Dr Haseltine speaks to Emily Culme-Seymour, Assistant Commissioning Editor William A Haseltine, PhD has an active career in both Science and Business. He was a professor at Harvard Medical School and Harvard School of Public Health (MA, USA) from 1976 to 1993, where he was Founder and Chair of two academic research departments. He is well known for his pioneering work on cancer, HIV/AIDS and genomics.