In-depth Bioinformatic Analyses of Human SARS-CoV-2, SARS-CoV, MERS-CoV, and Other Nidovirales Suggest Important Roles of Noncanonical Nucleic Acid Structures in Their Lifecycles

Martin Bartas; Václav Brázda; Natália Bohálová; Alessio Cantara; Adriana Volná; Tereza Stachurová; Katerina Malachová; Eva B. Jagelská; Otília Porubiaková; Jirí Cerven; Petr Pecinka

HNRNPA1 is known to bind and resolve G-quadruplex formed in TRA2B promoter and to promote its transcription. Dysregulation of this binding leads to progression of colon cancer. This interaction has been targeted by the well-known G-quadruplex stabilizer pyridostatin, which led to decreased transcription from the TRA2B promoter (Nishikawa et al., 2019) . Furthermore, HNRNPA1 is coexpressed with bromodomain and extraterminal domain protein BRD4 in human tumor samples. It has been shown experimentally that the well-described, naturally occurring polyphenolic flavonoid quercetin inhibited this protein and thereby led to better susceptibility to treatment in cancer patients (Pham et al., 2019) . Both SRSF7 and TRA2A proteins, which are predicted to interact with SARS-CoV-2 RNA, play roles in alternative splicing (Ghosh et al., 2016) . SRSF7 is a serine and argininerich splicing factor and is part of the spliceosome. Its expression has been connected to several types of cancer and it has been shown that its knockdown induced p21 expression and thus reduced cancer development (Saijo et al., 2016) . Little is known about TRA2A protein. It was first identified in insects together with its paralog TRA2B, which has been studied to a greater extent . It has . CC-BY-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.09.031252 doi: bioRxiv preprint been found that TRA2A can promote paclitaxel therapy and promote cancer progression in triplenegative breast cancers (Liu et al., 2017) . A role of TRA2A protein in regulation of HIV1 virus replication has been described. Both TRA2A and TRA2B bind to a specific HIV1 sequence and regulate its replication within the cell through alternative splicing of viral RNA (Erkelenz et al., 2013) .