Biology subjects

Manzourolajdad, A.

Publications and source records attributed to Manzourolajdad, A..

2 recordsLinked to original sources

bioRxiv2021

Evidence for a long-r ange RNA-RNA interaction between ORF8 and the downstream region of the Spike polybasic insertion of SARS-CoV-2

SARS-CoV-2 has affected people worldwide as the causative agent of COVID-19. The virus is related to the highly lethal SARS-CoV responsible for the 2002-2003 SARS outbreak in Asia. Research is ongoing to understand why both viruses have different spreading capacities and mortality rates. Like other beta coronaviruses, RNA-RNA interactions occur between different parts of the viral genomic RNA, resulting in discontinuous transcription and production of various sub-genomic RNAs. These sub-genomic RNAs are then translated into other viral proteins. In this work, we performed a comparative analysis for novel long-range RNA-RNA interactions that may involve the Spike region. Comparing predictions between reference sequences of SARS-CoV-1 and SARS-CoV-2 revealed several predictions amongst which a thermodynamically stable long-range RNA-RNA interaction between (23660-23703 Spike) and (28025-28060 ORF8) unique to SARS-CoV-2 was observed. Using data gathered worldwide, sequence variation patterns observed in the population support the in-silico RNA-RNA base-pairing predictions within these regions, suggesting further evidence for the interaction. The predicted interactions can potentially be related to the regulation of sub-genomic RNA production rates in SARS-CoV-2 and their subsequent accessibility to the host transcriptome.

bioinformatics↗

bioRxiv2021

Cellular abundance shapes function in piRNA-guided genome defense

Defense against genome invaders universally relies on RNA-guided immunity. Prokaryotic CRISPR/Cas and eukaryotic RNA interference pathways recognize targets by complementary base-pairing, which places the sequences of their guide RNAs at the center of self/nonself discrimination. Here, we explore the sequence space of PIWI-interacting RNAs (piRNAs), the genome defense of animals, and establish functional priority among individual sequences for the first time. Our results reveal that only the topmost abundant piRNAs are commonly present in every cell, while rare sequences generate cell-to-cell diversity in flies and mice. We identify a skewed distribution of sequence abundance as a hallmark of piRNA populations and show that quantitative differences of more than a thousand-fold are established by conserved mechanisms of biogenesis. Finally, our genomics analyses and direct reporter assays reveal that abundance determines function in piRNA-guided genome defense. Taken together, we identify an effective sequence space and untangle two classes of piRNAs that differ in complexity and function. The first class represents the topmost abundant sequences and drives silencing of genomic parasites. The second class sparsely covers an enormous sequence space. These rare piRNAs cannot function in every cell, every individual or every generation but create diversity with potential for adaptation in the ongoing arms race with genome invaders.

developmental biology↗