Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation

Myeloid leukocytes, such as neutrophils and monocytes, are critical for innate immunity. As splicing defects are common in malignancies that disrupt myeloid maturation, we hypothesise that alternative splicing (AS) programmes are important in regulating myelopoiesis. To study AS during human neu...

Full description

Saved in:
Bibliographic Details
Main Author: Sim, Donald Yuhui
Other Authors: Francesc Xavier Roca Castella
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2024
Subjects:
Online Access:https://hdl.handle.net/10356/175904
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-175904
record_format dspace
spelling sg-ntu-dr.10356-1759042024-06-03T06:51:19Z Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation Sim, Donald Yuhui Francesc Xavier Roca Castella School of Biological Sciences xroca@ntu.edu.sg Medicine, Health and Life Sciences RNA splicing Myeloid leukocytes, such as neutrophils and monocytes, are critical for innate immunity. As splicing defects are common in malignancies that disrupt myeloid maturation, we hypothesise that alternative splicing (AS) programmes are important in regulating myelopoiesis. To study AS during human neutrophil differentiation, HL-60 myeloid leukaemia cells were used as a model, where an increase in differential cassette exon events associated with non-productive mRNA isoforms was observed. Additionally, being primarily expressed in the neutrophilic and monocytic lineages among leukocytes, the role of the splicing factor RBM47 in myelopoiesis was examined, with HL-60 cells overexpressing RBM47 exhibiting enhancements in vitamin D3-induced monocytic differentiation and hundreds of AS changes. Furthermore, the re-analysis of human myeloid cell RNA-seq datasets revealed that exons neighbouring high GC-content introns were preferentially upregulated or downregulated in several datasets. Overall, several AS trends associated with myeloid maturation was examined, along with the putative myelopoietic regulatory role of RBM47. Doctor of Philosophy 2024-05-09T01:44:11Z 2024-05-09T01:44:11Z 2023 Thesis-Doctor of Philosophy Sim, D. Y. (2023). Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/175904 https://hdl.handle.net/10356/175904 10.32657/10356/175904 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Medicine, Health and Life Sciences
RNA splicing
spellingShingle Medicine, Health and Life Sciences
RNA splicing
Sim, Donald Yuhui
Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation
description Myeloid leukocytes, such as neutrophils and monocytes, are critical for innate immunity. As splicing defects are common in malignancies that disrupt myeloid maturation, we hypothesise that alternative splicing (AS) programmes are important in regulating myelopoiesis. To study AS during human neutrophil differentiation, HL-60 myeloid leukaemia cells were used as a model, where an increase in differential cassette exon events associated with non-productive mRNA isoforms was observed. Additionally, being primarily expressed in the neutrophilic and monocytic lineages among leukocytes, the role of the splicing factor RBM47 in myelopoiesis was examined, with HL-60 cells overexpressing RBM47 exhibiting enhancements in vitamin D3-induced monocytic differentiation and hundreds of AS changes. Furthermore, the re-analysis of human myeloid cell RNA-seq datasets revealed that exons neighbouring high GC-content introns were preferentially upregulated or downregulated in several datasets. Overall, several AS trends associated with myeloid maturation was examined, along with the putative myelopoietic regulatory role of RBM47.
author2 Francesc Xavier Roca Castella
author_facet Francesc Xavier Roca Castella
Sim, Donald Yuhui
format Thesis-Doctor of Philosophy
author Sim, Donald Yuhui
author_sort Sim, Donald Yuhui
title Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation
title_short Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation
title_full Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation
title_fullStr Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation
title_full_unstemmed Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation
title_sort analysis of alternative splicing profiles and the role of rbm47 in myeloid maturation
publisher Nanyang Technological University
publishDate 2024
url https://hdl.handle.net/10356/175904
_version_ 1806059820750471168