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10 results on '"Semler, Elizabeth M."'

2. 5‐Fluorouracil treatment represses pseudouridine‐containing miRNA export into extracellular vesicles.

Author

Qu, Shimian, Nelson, Hannah M., Liu, Xiao, Wang, Yu, Semler, Elizabeth M., Michell, Danielle L., Massick, Clark, Franklin, Jeffrey L., Karijolich, John, Weaver, Alissa M., Coffey, Robert J., Liu, Qi, Vickers, Kasey C., and Patton, James G.

Subjects
GENE expression, RNA modification & restriction, RNA metabolism, NON-coding RNA, EXTRACELLULAR vesicles
Abstract

5‐Fluorouracil (5‐FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5‐FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5‐FU on post‐transcriptional small RNA modifications (PTxMs) and the expression and export of RNA into small extracellular vesicles (sEVs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell‐cell communication. We found that treatment of colorectal cancer (CRC) cells with 5‐FU represses sEV export of miRNA and snRNA‐derived RNAs, but promotes export of snoRNA‐derived RNAs. Strikingly, 5‐FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5‐FU exposure led to increased levels of cellular small RNAs containing a variety of methyl‐modified bases. These unexpected findings show that 5‐FU exposure leads to altered RNA expression, base modification, and aberrant trafficking and localization of small RNAs. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Elucidation of physico-chemical principles of high-density lipoprotein-small RNA binding interactions

Author

Michell, Danielle L., primary, Allen, Ryan M., additional, Cavnar, Ashley B., additional, Contreras, Danielle M., additional, Yu, Minzhi, additional, Semler, Elizabeth M., additional, Massick, Clark, additional, Raby, Chase A., additional, Castleberry, Mark, additional, Ramirez, Marisol A., additional, Zhu, Wanying, additional, May-Zhang, Linda, additional, Ifrim, Anca, additional, Carr, John Jeffrey, additional, Terry, James G., additional, Schwendeman, Anna, additional, Davies, Sean S., additional, Sheng, Quanhu, additional, Linton, MacRae F., additional, and Vickers, Kasey C., additional

Published
2022
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7. Abstract 13914: Low-Density Lipoprotein Delivery of Microbial Small RNAs Drives Atherosclerosis Through Macrophage Toll-Like Receptor 8

Author

Allen, Ryan M, primary, Michell, Danielle L, additional, Cavnar, Ashley, additional, Zhu, Wanying, additional, Makhijani, Neil, additional, Contreras, Danielle M, additional, Raby, Chase, additional, Semler, Elizabeth M, additional, DeJulius, Carlisle, additional, Castleberry, Mark, additional, Zhang, Youmin, additional, Ramirez, Marisol, additional, Zhao, SHilin, additional, Duvall, Craig, additional, Doran, Amanda C, additional, Sheng, Quanhu, additional, Linton, Macrae F, additional, and Vickers, Kasey C, additional

Published
2021
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8. In Vitro Modeling Using Ciliopathy-Patient-Derived Cells Reveals Distinct Cilia Dysfunctions Caused by CEP290 Mutations

Author

Shimada, Hiroko, primary, Lu, Quanlong, additional, Insinna-Kettenhofen, Christine, additional, Nagashima, Kunio, additional, English, Milton A., additional, Semler, Elizabeth M., additional, Mahgerefteh, Jacklyn, additional, Cideciyan, Artur V., additional, Li, Tiansen, additional, Brooks, Brian P., additional, Gunay-Aygun, Meral, additional, Jacobson, Samuel G., additional, Cogliati, Tiziana, additional, Westlake, Christopher J., additional, and Swaroop, Anand, additional

Published
2017
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9. Darwin’s finches treat their feathers with a natural repellent

Author

Cimadom, Arno, primary, Causton, Charlotte, additional, Cha, Dong H., additional, Damiens, David, additional, Fessl, Birgit, additional, Hood-Nowotny, Rebecca, additional, Lincango, Piedad, additional, Mieles, Alejandro E., additional, Nemeth, Erwin, additional, Semler, Elizabeth M., additional, Teale, Stephen A., additional, and Tebbich, Sabine, additional

Published
2016
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10. In VitroModeling Using Ciliopathy-Patient-Derived Cells Reveals Distinct Cilia Dysfunctions Caused by CEP290Mutations

Author

Shimada, Hiroko, Lu, Quanlong, Insinna-Kettenhofen, Christine, Nagashima, Kunio, English, Milton A., Semler, Elizabeth M., Mahgerefteh, Jacklyn, Cideciyan, Artur V., Li, Tiansen, Brooks, Brian P., Gunay-Aygun, Meral, Jacobson, Samuel G., Cogliati, Tiziana, Westlake, Christopher J., and Swaroop, Anand

Abstract

Mutations in CEP290, a transition zone protein in primary cilia, cause diverse ciliopathies, including Leber congenital amaurosis (LCA) and Joubert-syndrome and related disorders (JSRD). We examined cilia biogenesis and function in cells derived from CEP290-LCA and CEP290-JSRD patients. CEP290 protein was reduced in LCA fibroblasts with no detectable impact on cilia; however, optic cups derived from induced pluripotent stem cells (iPSCs) of CEP290-LCA patients displayed less developed photoreceptor cilia. Lack of CEP290 in JSRD fibroblasts resulted in abnormal cilia and decreased ciliogenesis. We observed selectively reduced localization of ADCY3 and ARL13B. Notably, Hedgehog signaling was augmented in CEP290-JSRD because of enhanced ciliary transport of Smoothened and GPR161. These results demonstrate a direct correlation between the extent of ciliogenesis defects in fibroblasts and photoreceptors with phenotypic severity in JSRD and LCA, respectively, and strengthen the role of CEP290 as a selective ciliary gatekeeper for transport of signaling molecules in and out of the cilium.

Published
2017
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