Regulation of immune responses by RasGEF1B circular RNA / Ng Wei Lun

Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown f...

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Main Author: Ng , Wei Lun
Format: Thesis
Published: 2017
Subjects:
Online Access:http://studentsrepo.um.edu.my/8438/
http://studentsrepo.um.edu.my/8438/2/All.pdf
http://studentsrepo.um.edu.my/8438/6/wei_lun.pdf
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author Ng , Wei Lun
author_facet Ng , Wei Lun
author_sort Ng , Wei Lun
building UM Research Repository
collection Online Access
description Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown functions, or their production is spatially and temporally regulated to carry out specific biological functions. To date, the majority of circRNAs have been cataloged in resting cells. Here, this research identifies a LPS-inducible circRNA: mcircRasGEF1B, which is predominantly localized in cytoplasm, shows cell-type specific expression, and has a human homolog with similar properties, hcircRasGEF1B. The functional experiments show that knockdown of the expression of mcircRasGEF1B reduces LPS-induced ICAM-1 expression. Additionally, this study demonstrates that mcircRasGEF1B regulates the stability of mature ICAM-1 mRNAs. To gain broader insights of mcircRasGEF1B function during cellular response to LPS stimulation, targeted mcircRasGEF1B depletion with high-throughput transcriptomic analysis is combined. The results show that knockdown of mcircRasGEF1B results in altered expression of a wide array of genes. Pathway analysis reveals an overall enrichment of genes involved in cell cycle progression, mitotic division, active metabolism, and of particular interest, NF-κB, LPS signaling pathways and macrophage activation. These findings expand the inventory of functionally characterized circRNAs with a novel RNA species that may play a critical role in fine-tuning immune responses during macrophage activation and protecting cells against microbial infection.
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spelling um-84382020-06-23T23:43:32Z Regulation of immune responses by RasGEF1B circular RNA / Ng Wei Lun Ng , Wei Lun Q Science (General) QH301 Biology Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown functions, or their production is spatially and temporally regulated to carry out specific biological functions. To date, the majority of circRNAs have been cataloged in resting cells. Here, this research identifies a LPS-inducible circRNA: mcircRasGEF1B, which is predominantly localized in cytoplasm, shows cell-type specific expression, and has a human homolog with similar properties, hcircRasGEF1B. The functional experiments show that knockdown of the expression of mcircRasGEF1B reduces LPS-induced ICAM-1 expression. Additionally, this study demonstrates that mcircRasGEF1B regulates the stability of mature ICAM-1 mRNAs. To gain broader insights of mcircRasGEF1B function during cellular response to LPS stimulation, targeted mcircRasGEF1B depletion with high-throughput transcriptomic analysis is combined. The results show that knockdown of mcircRasGEF1B results in altered expression of a wide array of genes. Pathway analysis reveals an overall enrichment of genes involved in cell cycle progression, mitotic division, active metabolism, and of particular interest, NF-κB, LPS signaling pathways and macrophage activation. These findings expand the inventory of functionally characterized circRNAs with a novel RNA species that may play a critical role in fine-tuning immune responses during macrophage activation and protecting cells against microbial infection. 2017-12 Thesis NonPeerReviewed application/pdf http://studentsrepo.um.edu.my/8438/2/All.pdf application/pdf http://studentsrepo.um.edu.my/8438/6/wei_lun.pdf Ng , Wei Lun (2017) Regulation of immune responses by RasGEF1B circular RNA / Ng Wei Lun. PhD thesis, University of Malaya. http://studentsrepo.um.edu.my/8438/
spellingShingle Q Science (General)
QH301 Biology
Ng , Wei Lun
Regulation of immune responses by RasGEF1B circular RNA / Ng Wei Lun
title Regulation of immune responses by RasGEF1B circular RNA / Ng Wei Lun
title_full Regulation of immune responses by RasGEF1B circular RNA / Ng Wei Lun
title_fullStr Regulation of immune responses by RasGEF1B circular RNA / Ng Wei Lun
title_full_unstemmed Regulation of immune responses by RasGEF1B circular RNA / Ng Wei Lun
title_short Regulation of immune responses by RasGEF1B circular RNA / Ng Wei Lun
title_sort regulation of immune responses by rasgef1b circular rna / ng wei lun
topic Q Science (General)
QH301 Biology
url http://studentsrepo.um.edu.my/8438/
http://studentsrepo.um.edu.my/8438/2/All.pdf
http://studentsrepo.um.edu.my/8438/6/wei_lun.pdf