Asset Details
Do you wish to reserve the book?
ZAP isoforms regulate unfolded protein response and epithelial- mesenchymal transition
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
ZAP isoforms regulate unfolded protein response and epithelial- mesenchymal transition
Do you wish to request the book?
ZAP isoforms regulate unfolded protein response and epithelial- mesenchymal transition
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
ZAP isoforms regulate unfolded protein response and epithelial- mesenchymal transition
2022
Overview
Human ZAP inhibits many viruses, including HIV and coronaviruses, by binding to viral RNAs to promote their degradation and/or translation suppression. However, the regulatory role of ZAP in host mRNAs is largely unknown. Two major alternatively spliced ZAP isoforms, the constitutively expressed ZAPL and the infection-inducible ZAPS, play overlapping yet different antiviral and other roles that need further characterization. We found that the splicing factors hnRNPA1/A2, PTBP1/2, and U1-snRNP inhibit ZAPS production and demonstrated the feasibility to modulate the ZAPL/S balance by splice-switching antisense oligonucleotides in human cells. Transcriptomic analysis of ZAP-isoform–specific knockout cells revealed uncharacterized host mRNAs targeted by ZAPL/S with broad cellular functions such as unfolded protein response (UPR), epithelial-mesenchymal transition (EMT), and innate immunity. We established that endogenous ZAPL and ZAPS localize to membrane compartments and cytosol, respectively, and that the differential localization correlates with their target-RNA specificity. We showed that the ZAP isoforms regulated different UPR branches under resting and stress conditions and affected cell viability during ER stress. We also provided evidence for a different function of the ZAP isoforms in EMT-related cell migration, with effects that are cell-type dependent. Overall, this study demonstrates that the competition between splicing and IPA is a potential target for the modulation of the ZAPL/S balance, and reports new cellular transcripts and processes regulated by the ZAP isoforms.
Publisher
National Academy of Sciences
Subject
/ Cytosol
/ Epithelial-Mesenchymal Transition - genetics
/ Heterogeneous Nuclear Ribonucleoprotein A1 - metabolism
/ Heterogeneous-Nuclear Ribonucleoproteins - genetics
/ Heterogeneous-Nuclear Ribonucleoproteins - metabolism
/ HIV
/ Human immunodeficiency virus
/ Humans
/ Isoforms
/ Polypyrimidine Tract-Binding Protein - genetics
/ Polypyrimidine Tract-Binding Protein - metabolism
/ Protein Isoforms - metabolism
/ Proteins
/ Ribonucleoproteins (small nuclear)
/ Ribonucleoproteins, Small Nuclear - metabolism
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - metabolism
/ Splicing
