Lucas, J. S. | Search bioRxiv

bioRxiv2021

A Proposed Unified Interphase Nucleus Chromosome Structure: Preliminary Preponderance of Evidence

Cellular cryo-electron tomography (CET) of the cell nucleus using Scanning Transmission Electron Microscopy (STEM) and the use of deconvolution (DC) processing technology has highlighted a large-scale, 100-300 nm interphase chromosome structure (LSS), that is present throughout the nucleus. This chromosome structure appears to coil the nucleosome 11-nm fiber into a defined hollow structure, analogous to a Slinky (S) (1, motif used in 2) helical spring. This S architecture can be used to build chromosome territories, extended to polytene chromosome structure, as well as to the structure of Lampbrush chromosomes. Significance StatementCryo-preservation of the nuclear interior allows a large scale interphase chromosome structure--present throughout the nucleus--to be seen for the first time. This structure can be proposed to be a defined coiled entity, a Slinky. This structure can be further used to explain polytene chromosome structure, an unknown chromosome architecture as well as for lampbrush chromosomes. In addition, this new structure can be further organized as chromosome territories, using all 46 human interphase chromosomes as an example, easily into a 10 micron diameter nucleus. Thus, interphase chromosomes can be unified into a flexible defined structure.

cell biology↗

bioRxiv2020

A novel isoform of ACE2 is expressed in human nasal and bronchial respiratory epithelia and is upregulated in response to RNA respiratory virus infection

Angiotensin-converting enzyme 2 (ACE2) is the main entry point in the airways for SARS-CoV-2. ACE2 binding to SARS-CoV-2 protein Spike triggers viral fusion with the cell membrane, resulting in viral RNA genome delivery into the host. Despite ACE2s critical role in SARS-CoV-2 infection, an understanding of ACE2 expression, including in response to viral infection, remains unclear. Until now ACE2 was thought to encode five transcripts and one 805 amino acid protein. Here we identify a novel short isoform of ACE2. Short ACE2 is expressed in the airway epithelium, the main site of SARS-CoV-2 infection; it is substantially upregulated in response to interferon stimulation and RV infection, but not in response to SARS-CoV-2 infection, and it shows differential regulation in asthma patients. This short isoform lacks SARS-CoV-2 spike glycoprotein high-affinity binding sites and altogether, our data are consistent with a model where short ACE2 may influence host susceptibility to SARS-CoV-2 infection.

molecular biology↗