Ancient viral DNA in the human genome guards against infections

A recent paper published in Science reports that viral DNA in human genomes, embedded there from ancient infections, serve as antivirals that protect human cells against certain modern viruses. The researchers have scanned the human genome and uncovered many sequences with potential antiretroviral activity. Read more about this study under Article 1.

Article 1: Evolution and antiviral activity of a human protein of retroviral origin

This paper reports that viral DNA in human genomes, embedded there from ancient infections, serve as antivirals that protect human cells against certain modern viruses. Previous studies have shown that fragments of ancient viral DNA, called endogenous retroviruses encoding envelope proteins, in the genomes of several mammals provide immunity against modern viruses by blocking them from entering host cells. The researchers have scanned the human genome and uncovered many envelope-derived sequences with potential antiretroviral activity. They found that one envelope-derived protein called Suppressyn, which is expressed in the developing placenta and is capable of binding to a receptor for a wide number of retroviruses, could restrict infection by extant mammalian type D retroviruses. The team speculates that Suppressyn may have been preserved in the human genome for its ability to shield the early embryo and nascent germline from infection. Read the full article here.

In summary: Ancient viral DNA in human genome guards against infections

Article 2: How SARS-CoV-2 battles our immune system

This protein atlas graphic was assembled during the summer of 2022 based on the most current papers, preprints, and feedback from scientists. This atlas visualizes the latest SARS-CoV-2 information, including protein structures. However, as SARS-CoV-2 information continues to rapidly change, some information may therefore be out of date. Some protein structures were not fully available and were therefore predicted using either homology modeling, de novo modeling, artificial intelligence prediction, or inferred artistically based on similar molecules/other known structures. Enjoy scrolling through the atlas! Read the full article here.

In summary: The protein arsenal wielded by SARS-CoV-2

Article 3: Trio-based whole exome sequencing in patients with suspected sporadic inborn errors of immunity: a retrospective cohort study

This paper presents findings from a retrospective exome sequencing-based analysis of sporadic inborn errors of immunity cases. Based on protein-coding sequences for 123 suspected inborn errors of immunity patients along with corresponding exome sequences from their parents, the researchers found apparent genetic variants in a dozen of the inborn errors of immunity cases. They focused on 14 de novo variant candidates falling in inborn errors of immunity genes such as NLRP3 or RELA as well as other candidate genes with ties to the immune system. For example, they assessed a splice site change in FBXW11 in immune cells from an autoinflammatory disease patient and detected downstream signaling shifts and enhanced production of the pro-inflammatory cytokine interleukin IL-1-beta. Based on these and other findings, the researchers advocate the structural implementation of trio-based sequencing in the diagnostic evaluation of patients with sporadic inborn errors of immunity. Read the full article here.

In summary: Trio exomes to detect de novo variants in inborn errors of immunity

Article 4: Programmable eukaryotic protein synthesis with RNA sensors by harnessing ADAR

Leveraging advances in RNA editing, the researchers have developed a technique for triggering the production of specific proteins in live cells. The approach can be used for several applications, including tracking transcriptional states, RNA-sensing-induced cell death, cell type identification, and control of synthetic mRNA translation. The approach uses an RNA engineered to contain a guide region that binds to a target cellular RNA sequence and a region that encodes a protein of interest. When the guide RNA binds to its target, a short double-stranded RNA sequence containing an adenosine-to-cytosine mismatch is generated. This mismatch recruits a naturally occurring family of RNA-editing proteins called adenosine deaminases acting on RNA (ADARs), which inactivate a cellular stop signal blocking production of the desired protein, allowing for its translation. Importantly, the protein of interest is only produced after the guide RNA binds to its target and triggers the ADARs. The researchers show that the engineered RNAs, dubbed RADARS, can produce a range of proteins, including luciferases, fluorescent proteins, recombinases, and apoptosis-inducing caspases, and can distinguish between different cell types including kidney, uterine, and live cells. RADARS also measured gene expression over a large dynamic range, demonstrating their utility as sensors. “Overall, RADARS forms the basis of a reprogrammable biological sensor platform with many applications for biomedical research, diagnostics, and therapeutics,” they write. Read the full article here.

In summary: Reprogrammable biological sensor platform with many applications for biomedical research, diagnostics, and therapeutics

New in Genetics issue November 2022. Every month, Medicover Genetics curates the most important peer-reviewed scientific publications related to genetics.

References

[1] Frank JA et al. Evolution and antiviral activity of a human protein of retroviral origin. Science. 2022 Oct 28;378(6618):422-428. doi: 10.1126/science.abq7871. Epub 2022 Oct 27. PMID: 36302021. https://www.science.org/doi/10.1126/science.abq7871

[2] Leslie M. A viral arsenal. Science. 2022 Oct 14;378(6616):128-131. doi: 10.1126/science.adf2350. Epub 2022 Oct 13. PMID: 36227990. https://www.science.org/content/article/how-sars-cov-2-battles-our-immune-system

[3] Hebert A et al. Trio-based whole exome sequencing in patients with suspected sporadic inborn errors of immunity: a retrospective cohort study. Elife. 2022 Oct 17;11:e78469. doi: 10.7554/eLife.78469. Epub ahead of print. PMID: 36250618. https://elifesciences.org/articles/78469

[4] Jiang K et al. Programmable eukaryotic protein synthesis with RNA sensors by harnessing ADAR. Nat Biotechnol. 2022 Oct 27. doi: 10.1038/s41587-022-01534-5. Epub ahead of print. PMID: 36302988. https://www.nature.com/articles/s41587-022-01534-5